cord-000249-hkc4vbmj 2010 About 50 researchers working in the field of systems genetics using mouse genetic reference populations (GRP) participated in the meeting and exchanged their results, phenotyping approaches, and data analysis tools for studying systems genetics. Several groups addressed the complex genetics of metabolic functions and disorders using different mouse GRPs. Gudrun Brockmann reported on the mapping of QTLs for obesity in a specific mouse strain isolated in Berlin and the BXD congenic strain set (Neuschl et al. Ritsert Jansen and Pjotr Prins presented their approaches to integrate data from various phenotypic studies, encompassing gene expression, metabolome, and classical traits, and to develop new tools for advanced and improved mapping of QTLs (Jansen et al. The Collaborative Cross (CC) is currently being generated as a community resource for more sensitive and refined mapping of QTLs. The goal is to breed a large population of recombinant inbred strains starting from eight founder strains. cord-000261-ip32y0j5 2010 Following immunization, human CD19 + B cells were sorted based on surface CD27 expression, as a marker of memory phenotype, and the isotype of surface Igs. The sorted B cell populations were immortalized in vitro by retroviral transduction with human B cell lymphoma (BCL)-6 and BCL-XL genes and antigen-specific B cell clones were established and characterized. The obtained results provided the proof-of-concept for the usefulness of this generic approach based on HIS mice combined with immortalization of human B cells for the rapid and inexpensive development of human mAbs against a wide range of antigens. Since HIS mice contained broad naïve B cell repertoires, we analyzed the induction of human antigen-specific B cell responses after immunization with commercially available human vaccines. So far, humanized mouse models based on the transplantation of human HSC only -i.e. without additional human tissues -share these limitations, and immunization strategies result in the limited generation of class-switched antigen-specific B cell responses [14, 31, 32] . cord-000539-uh3q65we 2012 BACKGROUND: Acute respiratory distress syndrome (ARDS) induced by pandemic 2009 H1N1 influenza virus has been widely reported and was considered the main cause of death in critically ill patients with 2009 H1N1 infection. Mice infected with SD/09 virus showed typical ARDS symptoms characterized by 60% lethality on days 8–10 post-inoculation, highly edematous lungs, inflammatory cellular infiltration, alveolar and interstitial edema, lung hemorrhage, progressive and severe hypoxemia, and elevated levels of proinflammatory cytokines and chemokines. In the present mouse model, the number of leukocytes observed in the BALF of virus-infected mice significantly increased compared with the control mice on day 8 p.i. Different counts in BALF showed that the proportion of neutrophils dramatically increased. cord-001569-jd028cyg 2015 We demonstrate that central pathophysiologic events in ALI (inflammation, IL-1β levels, endothelial and alveolar epithelial barrier permeability, remodelling and fibrosis) are attenuated in the lungs of Vim(−/−) mice challenged with LPS, bleomycin and asbestos. Exposure to bleomycin resulted in a large increase in immune cells in the airspace of both WT and Vim À / À mice as assessed by flow cytometric analysis of whole-lung lysates ( Supplementary Fig. 3a ). All together, these results suggest that vimentin-expressing bone marrow-derived cells are important for bleomycin-induced activation of the NLRP3 inflammasome and pulmonary fibrosis. Studies with IL-1R1 À / À , MyD88 À / À , ASC À / À , Caspase-1 À / À and NLRP3 À / À mice have suggested that uric acid (induced by bleomycin), asbestos and silica are detected by the NLRP3 inflammasome in macrophages, likely leading to IL-1R1/MyD88 signalling in pulmonary epithelial cells, then to inflammation, neutrophil and lymphocyte recruitment and fibroblast activation 35 . cord-001675-9717nzr7 2015 Here we demonstrate that the Tie2-agonist tetrameric peptide Vasculotide improves survival in murine models of severe influenza, even if administered as late as 72 hours after infection; the benefit was observed using three strains of the virus and two strains of mice. While the drug had no effect on human lung endothelial proliferation (Supplemental Figure 8) , it significantly attenuated lung endothelial apoptosis in vitro in response to influenza virus, as assessed by cleavage of caspase-3 (Supplemental Figure 7c ); we observed a similar reduction in cleaved caspase-3 in lungs from infected mice who received Vasculotide (Supplemental Figure 7d ). First, these data strongly implicate failure of the lung endothelial barrier as the cause of death in murine models of severe influenza, as Vasculotide conferred a significant survival benefit against multiple strains of the virus in two strains of mice. cord-001958-2gt3fwpy 2016 Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. In the work described here, we demonstrate in mouse models that percutaneous inoculation of MVA elicited protective immune responses against lethal intranasal challenge with the Western Reserve (WR) strain of vaccinia virus, and at low doses of MVA, lower morbidity was recorded in mice that were vaccinated via the percutaneous route than in those immunized via the intramuscular or subcutaneous routes. In a preliminary experiment to investigate the utility of the percutaneous route for the delivery of MVA, we observed that MVA delivered by tail scarification, while statistically insignificant (p = 0.298), elicited a higher vaccinia-specific IgG response and protection in mice than the same dose (10 6 pfu) delivered by the intramuscular route (S1 Fig) . cord-002341-v4r5d26a 2016 To establish a novel mouse model for ZIKV infection, we compared the clinical, histological, and virological findings of male (group 1) and female (group 2) mice with dexamethasone immunosuppression and ZIKV inoculation with those of the appropriate controls (groups 3 to 8) (Table 1 ). The dexamethasone-immunosuppressed mice with ZIKV inoculation in our study developed disseminated infection with viremia and multi-organ involvement, including the brain, urogenital tract, intestine, liver, spleen, pancreas, heart, lung, and salivary gland as evident by ZIKV-NS1 protein expression on immunohistochemical staining and/or detectable viral load in these tissues. Our findings provided an additional explanation for the pathogenesis of fatal ZIKV infection, which has been proposed to be related to uncontrolled virus dissemination in previously described mouse models utilizing types I/II interferon-signaling-/receptor-deficient mice that were unable to mount a robust host innate immune response. cord-003315-r1wkx0ml 2018 cord-003389-0yh5k6jk 2018 title: Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum volvulus specific biomarkers, screening for new therapeutic approaches and potentially studying the human immune response to infection with O. Based on the hypothesis that there is a genetic basis for mouse susceptibility and resistance to infection, novel strains of CC mice have been identified that are susceptible to specific bacteria, viruses, and parasites of humans [18] [19] [20] [21] [22] [23] . volvulus larvae after developing in NSG mice with or without human cells was in the same order of magnitude as that reported for the recovery of adult filarial worms, where infections were initiated by larvae recovered directly from the insect vector. Infected HuSkMc mice or BLT mice were selected for this analysis so the biomarkers identified would develop in the presence of human cells thereby potentially enhancing their specificity. cord-003634-iq0e1qp1 2018 cord-004416-qw6tusd2 2020 HLI was more severe in mice receiving the 2-stage compared to the 1-stage ischemia induction procedure as assessed by LDPI (p = 0.014), and reflected in a higher ischemic score (p = 0.004) and lower average distance travelled on a treadmill test (p = 0.045). Mice undergoing the 2-stage HLI also had lower expression of angiogenesis markers (vascular endothelial growth factor, p = 0.004; vascular endothelial growth factorreceptor 2, p = 0.008) and shear stress response mechano-transducer transient receptor potential vanilloid 4 (p = 0.041) within gastrocnemius muscle samples, compared to animals having the 1-stage HLI procedure. In contrast, the most commonly used animal model for initial testing of novel therapies for PAD is a model of acute blood supply interruption through ligation or excision of the femoral artery (referred to here as the 1-stage hind limb ischemia (HLI) model) 14, 15 . cord-004663-a47pkh8q 1982 title: Ependymitis, leukoencephalitis, hydrocephalus, and thrombotic vasculitis following chronic infection by mouse hepatitis virus 3 (MHV 3) In semisusceptible mice, infection led first to a transient meningitis, ependymitis, and leukoencephalitis, followed by a permanent communicating hydrocephalus and, later on, to a chronic thrombotic vasculitis affecting meningeal and parenchymal vessels at the brain stem level. Identical lesions occurred in fully susceptible mice infected with a low dose of virus, but no neurologic disorder could be induced in genetically resistant mice even following immunosuppression or intracranial inoculation. When six susceptible BALB/c mice were injected i.p. with MHV 3 (103LD50), they died of an acute hepatic necrosis 5 -8 d a y s after M H V 3 infection, and no neuropatholigic lesion was observed except a slight degree of meningeal infiltration. cord-004774-fvf671jn 1985 cord-004879-pgyzluwp 1994 Furthermore kinetic experiments after complementation of HIV=RT p66 with KIV-RT pSl indicated that HIV-RT pSl can restore rate and extent of strand displacement activity by HIV-RT p66 compared to the HIV-RT heterodimer D66/D51, suggesting a function of the 51 kDa polypeptide, The mouse mammary tumor virus proviral DNA contains an open reading frame in the 3'' long terminal repeat which can code for a 36 kDa polypeptide with a putative transmembrane sequence and five N-linked glycosylation sites. To this end we used constructs encoding the c-fos (and c-jun) genes fused to the hormone-binding domain of the human estrogen receptor, designated c-FosER (and c-JunER), We could show that short-term activation (30 mins.) of c-FosER by estradiole (E2) led to the disruption of epithelial cell polarity within 24 hours, as characterized by the expression of apical and basolateral marker proteins. cord-006229-7yoilsho 2016 It directly activates Protein Kinase A (PKA) or the Exchange protein directly activated by cAMP (Epac) which is a guanine exchange factor (GEF) for the small monomeric GTPase Rap. As Human umbilical vein endothelial cells (HUVEC) express both cAMP effectors (Epac1 and PKA), we investigated the role of cAMP-signaling using a spheroid based sprouting assay as an in vitro model for angiogenesis. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration Methods and Results: Here we demonstrate that dexamethasone treatment lowered S1P 1 mRNA and protein expression levels in rat mesangial cells measured by TaqMan® and Western blot analyses. The aim of this study was to investigate the relevance of IGFBP5 in cardiogenesis and cardiac remodeling and its role as a potential target for ameliorating stress-induced cardiac remodeling Methods and Results: We investigated the expression of Igfbp5 in murine cardiac tissue at different developmental stages by qPCR normalized to Tpt1 (Tumor Protein, Translationally-Controlled 1). cord-006230-xta38e7j 2012 Here, we will present our analysis of Ca 2+ signaling following stimulation of the FcεRI receptor and application of secretagogues that are supposed to affect Ca 2+ -dependent mast cell activation such as adenosine, endothelin-1, substance P and compound 48/80 in BMMCs and PMCs derived from mouse lines with inactivation of TRPC1, TRPC3, TRPC4, TRPC5 or TRPC6 since specific antagonists are still lacking for these TRP channels. These data indicate that increased PP2A activity is associated with modified gene expression in TG hearts possibly affecting stress response and regulation of cell signalling. As demonstrated by qPCR and Western blot experiments, mesangial cells showed a marked time-and dose-dependent upregulation of CSE mRNA and protein levels after treatment with platelet-derived growth factor (PDGF-BB). The transcription factor cAMP response element (CRE)-binding protein (CREB) plays a critical role in regulating gene expression in response to activation of the cAMPdependent signaling pathway, which is implicated in the pathophysiology of heart failure. cord-006588-aavpj5r3 2000 First, the ÒanesthesiologicalÓ indication: one of the major goals of anesthesia is achievement of more (39, 52) , mice lacking the brain derived neurotropic factor BDNF (1), RET-protooncogene deÞcient mice with depressed ventilatory response (4), and endothelin-1 deficient mice with altered blood gas-values (e.g., signiÞcantly lower PO 2 than wild type littermates) and impaired respiratory response to hypoxia and hypercapnia (30) . The most obvious difference between spontaneous respiration and usual modes of mechanical ventilation (MV) are inverted pressure relations, with respect to ambient pressure, during the respiratory cycle: during spontaneous inspiration the expansion of the intrathoracic volume (mainly caused by contraction of the diaphragm and extension of the rib cage) generates a negative intrathoracic pressure and allows gas ßow into the lungs. A typical example for a ventilator-induced regional side effect is the mechanical hyperinßation of the murine lung, e.g., when large tidal volumes or high airway pressures are applied. cord-007094-ur9sz21s 2008 Preservation of mouse germ-plasm is achieved by cryopreservation of spermatozoa, embryos, or ovaries, and embryonic stem cells are used for the production of genetically engineered mice. In this article, we discuss regulations and practical issues in the shipping of live mice and mouse tissues, including spermatozoa, embryos, ovaries, and embryonic stem cells, and review work on microbial contamination of these biological materials. The importation paperwork for cryopreserved laboratory mouse tissues and cell lines is similar to that required for live animal importation to the United States (i.e., a pro forma invoice and declaration statements). Embryo transfer recipients in rederivation programs should be held in individually ventilated cages (IVCs 1 ) until testing shows that they are free of all unwanted microorganisms, including those listed in Appendix 3 of the Federation of Laboratory Animal Science Associations (FELASA) recommendations (Nicklas et al. Risk assessment of mouse hepatitis virus infection via in vitro fertilization and embryo transfer by the use of zona-intact and laser-microdissected oocytes cord-007726-bqlf72fe 2018 The laboratory mouse Mus musculus has long been used as a model organism to test hypotheses and treatments related to understanding the mechanisms of disease in humans; however, for these experiments to be relevant, it is important to know the complex ways in which mice are similar to humans and, crucially, the ways in which they differ. This chapter will provide an overview of the important similarities and differences between Mus musculus and Homo sapiens and their relevance to the use of the mouse as a model organism and provide specific examples of the quality of mouse models used to investigate the mechanisms, pathology, and treatment of human lung diseases. Overall, these studies showed that although gene expression is fairly similar between mice and humans, considerable differences were observed in the regulatory networks controlling the activity of the immune system, metabolic functions, and responses to stress, all of which have important implications when using mice to model human disease. cord-009388-k3exf8a4 2020 cord-010187-ymhcfyxx 2005 We report a comparison of the clinical course and the histopathological features of neurological disease resulting from intracerebral virus inoculation in normal micewith those of murine poliomyelitis in hPVR-tg mice. Histopathological analysis showed a diffuse encephalomyelitis induced by specific poliovirus serotype 2 isolates in normal mice, that affected neuronal cell populations without discrimination, whereas in hPVR-tg animals, damage was restricted to spinal motor neurons. 6 The hPVR is a highly glycosylated protein with an apparent molecular weight of 80kDa2 The animal model for poliomyelitis in hPVR-tg mice showed PV-induced damage of comparable anatomical distribution as in primates, 1°''11 an observation confirming views of the hPVR as the critical determinant conferring PV susceptibility. None of the normal mice injected with PVI(M) showed clinical signs of neurological damage, whereas inoculation of type 2 PV strains produced signs of CNS infection ( Table 2) . cord-010278-loey5xq9 1995 The structure of the mouse CstC-encoding gene (Cst3) was examined by sequencing a 6.1-kb genomic DNA containing the entire gene, as well as 0.9 kb of 5′ flanking and 1.7 kb of its 3′ flanking region. An exact match of nine nt with the pituitary transcription factor (Pit-l) recognition element is centered around nt -795 from the start codon, but is probably of low significance for the expression of the gene because multiple recognition elements have been shown to be needed for markedly increased expression of the rat prolactin gene by Pit-1 (Ingraham et al., 1988 recognized by the leader binding protein (LBP-1), 5''-WCTGG-3'' or its inverse, that is present in several copies in the HIV-1 promoter and contribute to its basal function (Jones et al., 1988) , is strikingly abundant in the 5''-flanking region of the mouse Cst3 gene. The presence of the two AP-l-like binding sites in the promoter indicates that Differences between the mouse Cst3 gene sequence and that of the published eDNA (Solem et al., 1990) Position" cord-013023-uanozm00 2020 We then optically stimulated cholinergic NBM fibers locally in the BLA, while mice learned to nose poke in response to an auditory cue to receive a food reward to determine if accelerating the increase in ACh signaling that occurs as mice learn the task would enhance performance. As in the previous experiment, there were no differences between the EYFP control (n = 6) and stimulation groups (contingent-ChR2 n = 5 and non-contingent ChR2 n = 5) during Pre-Training ( Figure These results demonstrate that ChR2-mediated ACh release does not have to be time-locked to the cue, nose poke, or reward retrieval to improve performance of the task, suggesting that ACh may alter the threshold for neuronal plasticity for cue-reward pairing over a much longer timescale than might be expected based on results from the ACh3.0 recording and NBM-BLA recordings, which could be consistent with the involvement of mAChR signaling in this effect. cord-015021-pol2qm74 1994 It is our current understanding that LPS is responsible for many of the pathophysiological events observed during gramnegative infections and that one of the major mechanisms leading to shock and death is the LPS-induced activation of macrophages resulting in the production and release of lipid and peptide mediators, among which tumor necrosis factor seems to be the most important. However plasma IL-6 estimation revealed a statistically significant reduction at 6 hours in tanrine-treated animals compared to glycino and TW controls ( Objective: To evaluate the effects of allogeneic blood transfusion, thermal injury and bacterial garage on interteukin 4 (IL-4), tumor necrosis factor alpha (TNF) production and host mortality and to study if the administration of thymopentth (THY) could affect these events. cord-015147-h0o0yqv8 2014 Cyclooxygenases (COX) catalyze the first step in the synthesis of prostaglandins (PG) from arachidonic acid.COX-1 is constitutively expressed.The COX-2 gene is an immediate early-response gene that is induced by variety of mitogenic and inflammatory stimuli.Levels of COX-2 are increased in both inflamed and malignant tissues.In inflamed tissues, there is both pharmacological and genetic evidence that targeting COX-2 can either improve (e.g., osteoarthritis) or exacerbate symptoms (e.g., inflammatory bowel disease).Multiple lines of evidence suggest that COX-2 plays a significant role in carcinogenesis.The most specific data that support a cause-and effect relationship between COX-2 and tumorigenesis come from genetic studies.Overexpression of COX-2 has been observed to drive tumor formation whereas COX-2 deficiency protects against several tumor types.Selective COX-2 inhibitors protect against the formation and growth of experimental tumors.Moreover, selective COX-2 inhibitors are active in preventing colorectal adenomas in humans.Increased amounts of COX-2-derived PGE2 are found in both inflamed and neoplastic tissues.The fact that PGE2 can stimulate cell proliferation, inhibit apoptosis and induce angiogenesis fits with evidence that induction of COX-2 contributes to both wound healing and tumor growth.Taken together, it seems likely that COX-2 induction contributes to wound healing in response to injury but reduces the threshold for carcinogenesis. cord-015569-vy49r1zd 2012 In this study, in order to test whether the cadherins are required for formation of synapse between gustatory nerve fibers and taste receptor cells, we have investigated expression patterns of cadherin superfamily in the taste buds. Therefore, this study aimed to examine differences in immunoreactivities under various tissue-preparing conditions in rat vallate taste buds for some typical markers of gustatory cells as follows: gustducin, type III inositol triphosphate receptor (IP 3 R3), synaptobrevin-2 (VAMP2), protein gene product 9.5 (PGP9.5), and neural cell adhesion molecule (NCAM). Mainly developing artificial-lipids-based taste sensors with global selectivity, our research group have studied for realization of Ã�taste-odor fusion biosensor system,Ã� which estimates quality (deliciousness and safety) of foods or beverages using several sensor outputs through analysis and evaluation of subjective-objective relation. As a first step, we conducted a series of human sensory tests to investigate perceptual similarities between odorants, and then compared the results with activity patterns evoked on the glomerular layer of the olfactory bulb in rats. cord-017521-z9l9c83i 2015 Neointimal formation consisted largely of SMC-like cells, similar to the case in the polyethylene cuff-induced injury. Mice overexpressing the murine HAS2 gene specifically in the vascular SMCs (cHAS2/CreSM22a mice) showed markedly enhanced cuff-induced neointimal formation, with augmentation of SMC migration and proliferation, and production of inflammatory cytokines and ROS [39] . iNOS has been shown to be expressed in the SMCs after cuff-induced vascular injury in rabbits [57, 58] , and iNOS-KO mice showed a significant reduction of neointimal thickening induced by cuff placement [59] . Application of Pam3Cys-SK4, a synthetic Tlr2 ligand, significantly enhanced the neointimal formation induced by cuff placement in the femoral arteries of the WT mice. In fact, AT1 receptor-KO mice showed decreased neointimal formation following cuff placement, accompanied by an increase of apoptotic cells among the SMCs [74] . On the other hand, neointimal formation induced by cuff placement was increased in AT2 receptor-KO mice. cord-021413-1ht1xm88 2013 Runner and Palm (1953) , studying C3H mice, indicated that there was a higher incidence of diarrhea in December/January (Kraft, 1961; Blackwell et al., 1966) , complement fixation (Wilsnack et al., 1969; Kapikian et al, 1976; Thouless et al., 1977b) , direct immunofluorescent staining or precipitin (Wilsnack et al., 1969; Spence et al., 1975; Foster α/., 1975; Peterson α/., 1976) , immune electron microscopy (Kapikian et al., 1974; Bridger and Woode, 1975) , immunoelectroosmophoresis (Tufvesson and Johnsson, 1976; Middleton et al., 1976) , enzyme-linked im munosorbent assay (ELISA) (Scherrer and Bernard, 1977; El lens etal., 1978; Yolken etal., 1978a,b,c) , radioimmunoas say (Acres and Babiuk, 1978; Kalica et al., 1977; Middleton et al., 1977) , immunodiffusion (Woode et al., 1976) , hemagglutination inhibition (Fauvel et al., 1978) , enzymelinked fluorescence assay (ELISA) (Yolken and Stopa, 1979) , an unlabeled soluble enzyme peroxidase-antiperoxidase method , plaque reduction test (Estes and Graham, 1980) , serologic trapping on antibody-coated electron microscope grids (Nicolaieff et al., 1980) , a solid phase system (SPACE, solid phase aggregation of coupled erythrocytes) for detection of rotaviruses in feces (Bradbume et al., 1979) , and immune electron microscopy with serum in agar diffusion (Lamontagne et al., 1980) . cord-021499-up5vftj4 2007 Depending on inoculation route, dose, strain, and age of mice, experimental infections may result in inflammation or cytomegaly with inclusion bodies in a variety of tissues, pneumonitis, myocarditis, meningoencephalitis, or splenic necrosis in susceptible strains (National Research Council, 1991; Osborn, 1982; Percy and Barthold, 2001) . Both strains are apathogenic for adult mice, but the immunosuppressive variant is more pathogenic for neonatal mice than is MMVp. Serological surveys show that the mouse is the primary natural host (Parker et al., 1970; Smith et al., 1993b; Singleton et al., 2000) , but the virus is also infective for rats, hamsters (Garant et al., 1980; Ward and Tattersall, 1982) , and Mastomys (Haag et al., 2000) during foetal development or after parenteral inoculation. Early descriptions of naturally occurring disease may have been complicated by concurrent infections such as MHV or murine rotavirus A (MuRV-A)/epizootic diarrhoea of infant mice (EDIM) virus that contributed to the severity of the lesions especially in liver, pancreas, CNS, and intestine. cord-022082-1dq623oe 2007 cord-022324-tcltmhi7 2012 cord-022353-q2k2krnm 2007 cord-022393-s26d54ew 2007 Wild caught mice that are maintained in naturalistic housing environments in the laboratory, laboratory mice that have contact with wild or feral mice, and mice kept as pets in the home environment are examples of animal management conditions that would be conducive to the expression and transmission of zoonotic diseases and other mouse-associated implications in the New World serocomplex group are present among the wild rodents endemic to the United States such as Neotoma spp. Many published reports of human LCM infection are associated with laboratory animal and pet contact, particularly mice and hamsters, and these studies now span many decades (Armstrong and Lillie 1934; Bowen et al. The apparent ease with which LCMV is transmitted to humans also occurs in a variety of other laboratory animal species; hamsters, guinea pigs, swine, dogs, and nonhuman primates, especially callitrichids, which readily sustain natural infections. akari infections depend on the prevention of wild mice and the mite vector from entering laboratory animal facilities and human dwellings. cord-022505-17khcmta 2018 Common microscopic findings in rodents that may be misinterpreted as lesions include: multinucleated, karyomegalic, and cytomegalic hepatocytes are common in several rodent species and can increase with age ( Fig. 20 .1); hepatocellular intranuclear cytoplasmic invaginations (pseudoinclusions) (Fig. 20 .1); eosinophilic cytoplasmic spherical inclusions in renal tubular epithelial cells and hepatocytes seen predominantly male mice, rats, and hamsters; splenic extramedullary hematopoiesis, which is very common in healthy rodents of all ages (Fig. 20 .2); hemosiderin, lipofuscin, ceroid, and melanin (in dark or black coated animals) are commonly detected in various tissues, such as spleen, liver, kidney, and adrenal glands; cardiac muscle in the tunica of pulmonary veins in the lung is a normal finding in mice; male rodents may have refluxed seminal coagula in the urinary bladder and urethra that is thought to occur peri mortem; and adrenal X-zone vacuolation in female mice. cord-022888-dnsdg04n 2009 Methods: Phospho-specific Western blot analyses were performed to verify the functionality of the different IFN-g pathway components, intra-and extracellular flow cytometry experiments were employed to determine the expression of antigen processing components and HLA class I cell surface antigens, quantitative real time-PCR experiments to confirm the absence of JAK2 and presence of pathway relevant molecules as well as, genomic PCR and chromosome typing technique to prove the deletion of JAK2. In order to accomplish these objectives we induced priming or tolerance of ovalbumin (OVA 323-339 peptide)-specific T cells from DO11.10 TCR transgenic mice in vitro or, following adoptive transfer of near physiologically relevant numbers of such cells into recipients, in vivo and correlated functional outcome (via proliferation and cytokine readout assays or antibody production) with E3 ubiquitin-protein ligases expression and the ubiquitination status of the TCR signalling machinery. cord-023026-2r84ndzv 2013 Thus, this work provides the basis to identify molecular pathways regulated by distinct niche/environmental signals and involved in the heterogeneity of adult OPCs. Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative demyelinating disease of the central nervous system (CNS) characterized by inflammation, which leads to formation of demyelinating areas due to loss of oligodendrocytes, astrogliosis and, finally, axonal degeneration. Taken together, these results demonstrate the important role of miR-200b in modulating the MAPK pathway via c-Jun which in turn affects different aspects of the inflammatory process accompanying microglia activation including cytokine response, NO production, phagocytosis and neuronal cell death. For this purpose, coronal cryostat free-floating sections from the brain of both adult transgenic mice and their corresponding wild-type (Wt) littermates, were processed for the study of astrocytes using GFAP immunohistochemistry and microglia using antibodies against Iba1 and several markers commonly related to the activated phenotype of these microglial cells, such as CD16/32 (Fc receptor), F4/80, CD11b, CD206, CD150 and MHC-II. cord-023055-ntbvmssh 2004 Antigen is internalized into acidic vesicles, proteolyzed, and peptides containing T ceU antigenic determinants are transported to the APC surface where they are recognized by the antigen-specific T cell in conjunction with Ia. Most Ia-"pressing cells are competent APC, however, only B cells have antigen-specilic receptors on their surface aUowing bound antigen to be processed and presented at 1/lW the antigen concentration required by nonspecific APC Little is known about B cell antigen processing function during differentiation, or if Ig-mediated APC function is altered at different maturational stages, thus allowing regulation of B cell-helper T cell interactions. These results indicate that the poor response of murine CTL to human class I antigens is not determined by selection in the thymus, but by species-specific constraints on the interaction of MHC antigens with T-cell recognition structures. cord-023143-fcno330z 2004 Based on a variety of experimental evidence, it is clear that demyelination induced in SJUJ mice by infection with the BeAn strain of TMEV is a Thl-mediated event: (a) disease induction is suppressed in T cell-deprived mice and by in vivo treatment with anti-I-A and anti-CD4 antibodies; (b) disease susceptibility correlates temporally with the development of TMEV-specific, MHC-class Il-restricted DTH responses and with a predominance of anti-viral lgG2a antibody; (c) activated (Le., lL-2RC) T cells infiltrating the CNS are exclusively of the CD4+ phenotype, and (d) proinflammatory cytokines (IFNq and TNF-p) are predominantly produced in the CNS. These results have important implications for a possible viral trigger in MS as they indicate that chronic demyelination in TMEV-infected mice is initiated in the absence of demonstrable neuroantigen-specific autoimmune responses and are consistent with a model wherein early myelin damage is mediated via primarily by mononuclear phagocytes recruited to the CNS and activated by pro-inflammatory cytokines produced by TMEV-specific Thl cells. cord-026009-rdhuc2n2 2009 cord-031279-8rckjc41 2020 cord-032975-7hugs419 1991 Nasal lesions were observed in all ferrocene-exposed animals and differed only in severity, which was dependent on the exposure concentration. In vitro metabolism studies of ferrocene showed that nasal tissue, particularly the olfactory epithelium, had 10 times higher "ferrocene hydroxylating" activity than did liver tissue from the same animals. Relative to control mice, male rats exposed to the highest concentration of ferrocene (40 mg/m 3 ) had statistically significant decreases in terminal body weight and rate of weight gain during the exposures. Male rats exposed to the highest concentration of ferrocene vapor had a statistically significant, although small, decrease in liver weights, compared to control animals. Similar nasal lesions were found in rats exposed to ferrocene vapor. We did not observe sex-related differences, and the severity of the lesion occurring after exposure to a given ferrocene concentration was about the same in rats and mice. cord-032982-xri24v40 1990 cord-103703-t03r6ny8 2020 title: Reduced expression of TCF7L2 in adipocyte impairs glucose tolerance associated with decreased insulin secretion, incretins levels and lipid metabolism dysregulation in male mice Mice with biallelic Tcf7l2 deletion exposed to high fat diet for 9 weeks exhibited impaired glucose tolerance (p=0.003 at 15 min after glucose injection) which was associated with reduced in vivo glucose-stimulated insulin secretion (decreased 0.51 ± 0.03-fold, p=0.02). Therefore, alterations in pancreatic beta cell function observed ex vivo in the absence of TCF7L2 in adipocyte have no impact on whole body glucose-stimulated insulin secretion. A striking finding in the present study is that TCF7L2 is required in adipose tissue for normal incretin production and insulin secretion: we reveal that decreased Tcf7l2 expression in mature adipocytes leads to lowered circulating levels of GLP-1 and GIP ( Fig.4a and b) . cord-104092-yau3r79c 2019 cord-104251-cq8ojfit 1981 cord-253459-tcn10pho 2020 4 A transgenic mouse model to study SARS-CoV-1 infection was developed that expresses the hACE2 gene under the control of the human cytokeratin 18 promoter. To investigate the potential of this transgenic mouse strain as a model for COVID-19 infection, five K18-hACE2 mice were intranasally inoculated with 8 × 10 4 Median Tissue Culture Infectious Dose (TCID50) of SARS-CoV-2, and five mice were mock-infected with sterile Dulbecco''s Modified Eagle''s Medium (DMEM). In the mouse model expressing hACE2 under the mouse ACE2 promoter, infected mice did not exhibit any clinical symptoms other than maximal weight loss on day 3 postinfection, and those mice recovered. 10 In contrast to these models, in which mice exhibited mild symptoms and recovered, only 60% of the mice survived past day 5 in the mouse strain expressing hACE2 under the lung ciliated epithelial cell HFH4 promoter. cord-254155-860780z9 2020 cord-254190-bxfne94u 2015 cord-254950-y6kayxie 1988 Abstract Mouse thymic virus (MTLV; murid herpesvirus 3) is a lymphotropic herpesvirus that cytolytically infects developing T lineage lymphocytes in the thymus of neonatal mice. In order to determine whether T lineage lymphocytes are required for infection, young adult athymic nude (nulnu) mice and euthymic littermates were infected with MTLV and tested for virus shedding. To determine whether MTLV infection requires thymus-derived lymphocytes, 4-week-old female ICR Swiss athymic nude (nulnu) and euthymic (+lnu) littermate controls (four each; Memorial Sloan-Kettering Cancer Center nude mouse breeding colony) were inoculated intraperitoneally with either 40 or 200 IDS0 of MTLV and virus shedding was tested by mouth swabs beginning 6 days after infection. litters available did not allow every negative sample to be tested, additional litters of normal newborn mice were inoculated with fresh homogenates (1 O-20%, w/v) of randomly selected negative thymuses and salivary glands, representing various test dates up to Day 48, from 14 assay litters that had received swab fluids from nude mice. cord-256903-8lyw27gh 2018 Dendritic cells (DC) as such, and their role in immunity were first described in the 1970s and in 1995 Ralph Steinman published a series of papers describing that a cellular receptor called "DEC-205" (now CD205) was expressed on mouse DC, was involved in antigen processing (58, 59) and was detected by the monoclonal antibody NLDC-145. Studies in mice, for example, have shown the efficacy of vaccines against FMDV, however these efficacy studies have failed to be translated to the target species (cattle and pigs), presumably due to fundamental differences in the immune systems of model organisms and target species and the ability of the virus to mutate in these animals (112) . The role of bovine γδ T cells and their WC1 co-receptor in response to bacterial pathogens and promoting vaccine efficacy: a model for cattle and humans cord-256998-or73in8m 2020 Among the more notable responses in other early preclinical studies, nearly half of mice bearing established B16F10 melanomas experienced complete tumor regression following 2 weekly treatments with pIL-12+EP (124) . In preclinical studies, a single intratumoral injection of mRNA encoding murine IL-12 (mIL-12) increased IFNγ expression and genes associated with a Th1 response in MC38 tumor-bearing mice (190) . In a useful comparison against other cytokines, one study demonstrated that Ad-IFN-γ had no greater antitumor activity than an empty Ad vector, whereas AdmIL-12 induced complete regressions of P815 mastocytomas in >80% of treated mice (219) . Antitumor activity on xenografts of human lung tissues indicated that liposomal encapsulation is a promising approach capable of eliminating tumor cells and inducing lymphocyte infiltration 2 weeks after i.t. injection. Immunotherapy of established tumors in mice by intratumoral injection of an adenovirus vector harboring the human IL-2 cDNA: induction of CD8 + T-cell immunity and NK activity cord-257167-rz4r5sj7 2006 SY1-3-11-3 SAD: A novel kinase implicated in phosphoproteome at the presynaptic active zone Toshihisa Ohtsuka Department of Clinical and Molecular Pathology, Faculty of Medicine/Graduate School of Medicine, University of Toyama, Toyama, Japan SAD is a serine/threonine kianse, which has been shown to regulate various neuronal functions during development, including clustering synaptic vesicles, maturation of synapses, and axon/dendrite polarization: these have recently been revealed by genetic studies in C. The results suggest that EAAT4 plays a major role in regulating the concentration of CF transmitters, possibly glutamate, in the route of its extrasynaptic diffusion, and determining the degree of CF-induced inhibition of GABA release from BCs depending on the regional difference of EAAT4 expression in postsynaptic PCs. Chitoshi Takayama 1 , Yoshiro Inoue 1 1 Department of Molecular Neuroanatomy, Hokkaido University School of Medicine, Sapporo, Japan GABA mediates inhibitory transmission in the adult central nervous system (CNS). cord-258129-c38q6xxs 2014 cord-261036-zdhg4axx 2010 cord-262445-54ng7m92 2020 cord-264408-vk4lt83x 2017 Well-developed animal models are necessary to understand disease progression, pathogenesis, and immunologic responses to viral infections in humans. NHPs including marmosets, cotton-top tamarins, and rhesus macaques infected with Norwalk virus are monitored for the extent of viral shedding; however, no clinical disease is observed in these models. Intracerebral and IN routes of infection resulted in a fatal disease that was highly dependent on dose while intradermal (ID) and subQ inoculations caused only 50% fatality in mice regardless of the amount of virus (liu et al., 1970) . Ferrets infected with Hendra or Nipah virus display the same clinical disease as seen in the hamster model and human cases (Bossart et al., 2009; Pallister et al., 2011) . Characterization studies with IFNAr −/− mice challenged with different routes (IP, IN, IM, and subQ) showed that CCHFV causes acute disease with high viral loads, pathology in liver and lymphoid tissues, increased proinflammatory response, severe thrombocytopenia, coagulopathy, and death, all of which are characteristics of human disease . cord-265299-oovkoiyj 2016 cord-265847-oq34lc26 1986 cord-266745-jit1xeqc 2010 title: Passive protection effect of chicken egg yolk immunoglobulins on enterovirus 71 infected mice The results of the neutralization effect of specific IgY in EV71-challenged mice demonstrate that the EV71-specific IgY, either by intraperitoneal injection or oral administration, was able to significantly reduce the morbidity and mortality in EV71 infected mice pups. This study was subjected to produce IgY against enterovirus 71 (anti-EV71 IgY) and evaluated the inhibition effects of specific IgY on EV71, including in vitro virus neutralization test and in vivo ICR mice model. In trial 1, we challenged 1-day-old mice with a mouse-adapted EV71 strain MP4 by intraperitoneally administering a dosage of 10 5 pfu per mouse, and treated with specific IgY of neutralization titer 64. This indicates that the orally fed specific IgY effectively neutralized the viral attack in the gastroenteric duct, thereby blocking the infection of virus in challenged mice. cord-267482-afqfymbq 2020 Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Also, initial studies that employ lung ciliated epithelial cell-specific HFH4/FOXJ1 promoter driven hACE2 transgenic mice show SARS-CoV-2 infection induces weight loss, lung inflammation and approximately 50% mortality rate, suggesting the usefulness of this model to understand the mechanism of immune dysregulation (Jiang et al., 2020) . Moreover, given our recent findings that ketogenesis inhibits inflammation and expands tissue resident ϒδ T cells (Goldberg et al., 2019) while SARS-CoV-2 infection in patients is associated with depletion of ϒδ T cells (Lei et al., 2020; Rijkers et al., 2020) , we next tested whether elevating BHB by feeding a ketogenic diet (KD) protects against mCoV-A59-driven inflammatory damage in aged mice. cord-267671-ys43n672 2015 Clinical Signs MCMV causes subclinical infection in adult immunocompetent mice, but experimental inoculation of neonates can cause lethal disease due to multisystemic necrosis and inflammation. Diagnosis Because infected mice do not manifest signs or lesions and the virus is very difficult to propagate in cell culture, detection and diagnosis rely on serology and molecular methods. Differential Diagnosis Reovirus infection must be differentiated from other diarrheal diseases of infant mice, including those caused by mouse coronaviruses, EDIM virus, Salmonella spp., or Clostridium piliforme. Epizootiology EDIM virus appears to be infectious only for mice and occurs episodically in mouse colonies, and infection is probably widespread geographically (Livingston and Riley, 2003; Pritchett-Corning LABORATORY ANIMAL MEDICINE et al., 2009) . Sentinel mouse surveillance, using soiled bedding, is an effective strategy for detecting MNV (Manuel et al., 2008) Differential Diagnosis The mild change in fecal consistency associated with MNV in adult mice may mimic rotavirus, coronavirus, Helicobacter spp., Citrobacter rodentium, or other enteric diseases. cord-267965-84sotgds 2019 cord-278136-ol2buwld 2016 cord-281161-u896icp9 2012 We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. As shown in Table 2 , similar IgG1 and IgG2a humoral immune responses against the influenza viruses were induced in the mice vaccinated previously with rRBD plus rOv-ASP-1 adjuvant and those administered with PBS only. As shown in Table 3 , all of the NHPs vaccinated with rRBD protein plus 50 mg (n = 2), 100 mg rOv-ASP-1 (n = 2) or 500 mg CpG (n = 1) as the adjuvant developed RBDspecific IgG antibody response with increasing antibody level after each boost. Secondly, using two concentration of the rOv-ASP-1 adjuvant, 50 or 100 mg, and rRBD as the vaccine antigen, we were able to induce after three immunizations high titers of neutralizing antibodies (1:3,500-1:6,392) that much exceed what is needed for protection against SARS-CoV infection in vivo (.1:500) [56] . cord-281410-y558a5jf 1981 cord-287527-ep6ug9c3 2018 title: Elevated Human Dipeptidyl Peptidase 4 Expression Reduces the Susceptibility of hDPP4 Transgenic Mice to Middle East Respiratory Syndrome Coronavirus Infection and Disease Specifically, we determined values of 50% lethal dose (LD(50)) of MERS-CoV for the 2 strains of mice, compared and correlated their levels of soluble (s)hDPP4 expression to susceptibility, and explored recombinant (r)shDPP4 as an effective MCM for MERS infection. ELISA-based and Vero E6 cell-based microneutralization assays, previously described [7] , were used to determine the titers of MERS-CoV RBD-specific serum IgG and neutralizing antibodies in hDPP4 Tg mice in response to MERS-CoV infection. Finally, we showed that administration with functionally active rhsDPP4 proteins (Figure 3 ) enabled hDPP4 +/− mice to better resist MERS-CoV infection in a dose-dependent manner (Table 1) , a finding in accordance with increased levels of shDPP4 in their circulation. cord-287670-z6ckhkgg 2016 cord-288133-h3wmo0xj 2017 cord-288253-wqrhiq08 2015 Because the major pathological changes of the porcine coronaviruses (e.g., TGEV and PEDV) involves enteric diseases, we measured porcine APN expression in the small intestine by RT-PCR, immunoblotting, and IHC. An immunohistochemical analysis, with both anti-Flag and anti-porcine APN antibodies, clearly confirmed porcine APN expression in the brush borders of the absorptive cells in the small intestines of the mouse model (Fig. 4C) . For these purposes, many transgenic mouse models have been developed to study viral pathogenesis, immune responses, and vaccines (Darling et Both wild type and porcine APN transgenic mice were infected with PEDV (5X TCID5010 6 ) orally on day 0. Although significant clinical illness was not observed when the transgenic mice were infected with PEDV, their susceptibility to the virus was confirmed by the detection of viral RNA in various organs with RT-PCR and viral proteins in the small intestines with IHC. cord-292157-hrm69640 2020 Typhimurium infection and antibiotic treatment failure, we assessed the potential of two consecutive doses of vitamin A in alleviating infection in male and female mice on a VAD or control diet. We found that subtherapeutic antibiotic treatment synergized with vitamin A treatment in infected VAD male mice, significantly decreasing systemic bacterial levels, mitigating weight loss and improving survival. Typhimurium systemic bacterial levels (CFU) were assessed for male (n = 5) and female (n = 5) mice on a standard diet 5 days post-infection for the following treatment groups: 0 mg/ml, 0.01 mg/ml, 0.05 mg/ml, and 0.10 mg/ml enrofloxacin delivered in the drinking water. Typhimurium D23580 at day 4 post-infection were assessed for male and female mice on either control or VAD diets with the following treatment groups: mocktreated, vitamin A only, enrofloxacin (0.05 mg/ml) only, and vitamin A and enrofloxacin cotreatment (Fig 5A) . cord-292402-u3sfc1yz 2016 Furthermore, virus antigens in fibrous structures reported in our previous study 17, 18 were found to colocalize with laminin and ERag ( Fig. 1F ) with almost the same image observed in the spleen of mice infected with LCMV, 33 which indicated that viruses are concentrated in the narrow space of reticular fibers 33, 43 and are recognized by immunofluorescence, and they use the reticular conduit system as a scaffold. The expression of ERag was either colocalized with that of components of the extracellular matrix (ECM) such as laminin (Fig. 1D ) and collagen (Fig. 1E ) in the same way as reticular fibers reported in lymphoid organs, 33 or found without such colocalization as shown in the brain parenchyma ( Fig. 1D2 and D3) and trigeminal root (Supplemental Figure S1A ). cord-292596-ulu5y140 2020 cord-295194-xbla6tu7 2020 cord-298117-9ycl7mn6 2018 cord-299605-j1ewxk4q 2017 cord-300372-h5g4z8ts 2014 cord-303662-ro9879dl 1990 Un-In view of the finding that whole body irradiairradiated mice demonstrated intense disease at tion at day 6 p.i. prevents JHMV-induced paraday 9 p.i. By contrast, mice given 850 rad at day 6 lytic-demyelinating disease, differential irradiation p.i. had few histological changes at day 9 p.i. In studies were conducted to determine whether critiaddition, a second mouse strain, BALB/cJ mice cal radiosensitive targets reside in the systemic or a Immune donor mice were 6-week-old C57BL/6J males given 106 PFU of JHMV 2.2-V-1 i.p. 6 days prior to transfer. These they resemble the original JHMV isolates, which experiments indicate that populations of murine in early passages primarily caused a nonfatal paradonor spleen cells, which are enriched for T lytic disease (Bailey et al., 1949; Cheever et al., lymphocytes and appear to be MHC-restricted, 1949) ; only after many i.c. passages did the virus restore demyelination to infected, irradiated re-acquire marked neurovirulence. cord-304855-7v0cncid 2009 cord-306516-5t3ix35e 2016 RESULTS: Calpastatin overexpression ameliorated myocardial injury induced by CVB3 infection significantly in transgenic mouse indicated by reduced peripheral CK-MB and cTnI levels and improved histology injury. In the transgenic mouse''s heart, calpain inhibition was accompanied with significant perforin down-regulation post virus infection (Fig. 3B) . This study, utilizing a calpastatin-overexpression transgenic mouse model of viral myocarditis, demonstrated that endogenous calpain inhibition ameliorated myocardial injury significantly. In our former study, we found that CVB3-induced calpain activation facilitates the progeny virus replication in the early phase of infection in vitro [6] . We presented here in CVB3-induced myocarditis model that myocardium inflammation infiltration was significantly ameliorated in transgenic mouse, as well as the inflammation factors of MPO activity, IL17, perforin and IFNγ. Coxsackievirus B3-induced calpain activation facilitates the progeny virus replication via a likely mechanism related with both autophagy enhancement and apoptosis inhibition in the early phase of infection: an in vitro study in H9c2 cells cord-306535-j26eqmxt 2020 The majority of candidate genes identified in our screen that were testis-specific were already identified by the Human Protein Atlas [9] and/or our reanalysis of (See figure on previous page.) Fig. 1 Summary of the human and mouse RNA-seq samples used in the identification of novel male reproductive tract-specific drug targets. Additional file 14: Fig. S6 shows the complete list of male reproductive tract-specific human genes for which a previously generated mouse model shows male infertility phenotype, as identified in each of the respective cell and/or tissue datasets. Through the integration of hundreds of published and newly acquired human and mouse reproductive and non-reproductive tissue and cell RNA-seq datasets, we have generated a list of novel genes expressed predominantly or exclusively in the male reproductive tract that are worthy of consideration for functional validation in an animal model and potential targeting for a male contraceptive. cord-308461-4lhh3du0 2020 Unlike ex vivo methods, which involve isolated or sliced lungs, in vivo imaging using two-photon excitation microscopy of live animals enables researchers to observe hemodynamics, migration and extravasation of immune cells, as well as interactions among immune cells during influenza virus infection. To detect multiple fluorescent signals excited simultaneously by a two-photon excitation laser, fluorochromes with different spectra and equal brightness must be selected; however, there is currently no comprehensive database of fluorescent reagents, fluorescent reporter viruses, and reporter mouse lines available for lung in vivo imaging. Our system uses suction-based lung stabilization 16, 28 to improve an existing in vivo two-photon imaging system for influenza virus-infected lung as a model of an acute inflammatory respiratory disease 5 . In vivo two-photon imaging is performed under conditions of single stimulation with a two-photon excitation laser; limitations exist regarding available fluorescent reagents/proteins for multiple labeling of target cells and lung architecture. cord-312305-ll29frwc 2020 cord-312692-jv3425w1 2019 cord-314333-hkyiy1gm 2008 title: Mouse-Passaged Severe Acute Respiratory Syndrome-Associated Coronavirus Leads to Lethal Pulmonary Edema and Diffuse Alveolar Damage in Adult but Not Young Mice Adult mice showed early and acute excessive proinflammatory responses (ie, cytokine storm) in the lungs after SARS-CoV infection, which led to severe pulmonary edema and diffuse alveolar damage. Because advanced age is associated with higher mortality in human SARS patients and SARS-CoV replicates better in aged mice, 6 -10,29 we experimentally infected 6-month-old (adult) female BALB/c mice with F-musX-VeroE6 or the Frankfurt 1 isolate. With regard to the cytokine responses of the mice, the lung homogenates of adult mice on day 1 after inoculation had significantly higher levels of monocyterelated chemokines [ie, MCP-1, macrophage inflammatory protein 1 (MIP-1), and IFN-␥-inducible protein 10 (IP-10)] than those from young mice ( Figure 5 ). cord-319933-yp9ofhi8 2013 An experimental study with cell culture-adapted hepatitis Avirus in guinea pigs challenged by oral or intraperitoneal routes did not result in clinical disease, increase in liver enzymes, or seroconversion. 32 NHPs including marmosets, cotton-top tamarins, and rhesus macaques infected with Norwalk virus can be monitored for the extent of viral shedding; however, no clinical disease is observed in these models. 66, 67 Intracerebral and intranasal routes of infection resulted in a fatal disease that was highly dependent on dose, while intradermal and subcutaneous inoculations caused only 50% fatality in mice regardless of the amount of virus. A mouse-adapted (MA) strain of Dengue virus 2 introduced into AG129 mice developed vascular leak syndrome similar to the severe disease seen in humans. [138] [139] [140] [141] [142] [143] [144] Inoculation of WNV into NHPs intracerebrally resulted in the development of either encephalitis, febrile disease, or an asymptomatic infection, depending on the virus strain and dose. cord-320172-qw47pf9r 2000 In common with other changes induced in the digestive tract of rats and cynomolgus monkeys by the administration of recombinant human epidermal growth factor, the tongue showed squamous epithelial hyperplasia characterised by a uniform increase in the thickness of the squamous epithelium in both species (Breider et al., 1996; Reindel et al., 1996) . Detailed study of hypertrophy, protein synthesis, and intracellular cAMP activity in the salivary glands of rats treated for 10 days with isoprenaline (isoproterenol), a series of β-adrenergic receptor agonists and the phosphodiesterase inhibitors, theophylline and caffeine, showed that similar effects occurred with all agents although differences in the degree of hypertrophy, the nature of pro-tein and glycoprotein synthesis and Golgi membrane enzyme activity were recorded (Wells and Humphreys-Beher, 1985) . Studies in the rat have shown that diffuse atrophy of the gastric glands characterised by a decrease in the number and size of parietal, chief and mucous cells occurs transiently following truncal vagotomy but histological features return to normal by about 1 month after surgery (Nakamura, 1985) . cord-324326-q014b5ym 2017 cord-324617-yok7mh70 2020 cord-326223-q6e60nf8 2005 cord-327568-5vo4nmei 2019 title: Delivery of SA35 and SA40 peptides in mice enhances humoral and cellular immune responses and confers protection against Cryptosporidium parvum infection parvum proteins, were tested for their ability to induce immune responses in adult mice and for protection on neonate BALB/c mice born from females immunised by mucosal delivery of both peptides. The IP immunisation of adult BALB/c mice to a single antigen (SA35 or SA40) or to a mixture of the two antigens (SA35/40 mix) induced specific anti-Cryptosporidium IgG in serum after day 14 following initial administration. The mucosal delivery of SA35/40 mix in female BALB/c mice induced specific anti-Cryptosporidium IgG (mainly IgG1) in serum 21 days after initial immunisation. In humans, maternal immunisation with tetanus toxoid has Fig. 9 Quantification of COWP gene DNA copies by qPCR in the intestinal content of neonate mice infected with 5 × 10 3 Cryptosporidium parvum oocysts. cord-329061-1xut73dq 1972 The virus that causes sialodacryoadenitis in rats has been isolated in mice and in primary cultures of rat-kidney cells and has been characterized as a heat-labile RNA virus that is sensitive to lipid solvents and is relatively stable at pH 3.0. Rats were inoculated intranasally with 0.1 ml of virus-infected salivary-gland suspension, observed daily for evidence of overt illness, and sacrificed at various intervals. Monolayers obtained from explant cultures of submaxillary, parotid, Harderian, and exorbital glands of germfree rats, monolayers of trypsin-dispersed brain cells of infant mice, and a line of polyoma-transformed mouse cells (Py-AL/N) [6J were also tested. The neutralization (N) test with sera immune to murine viruses was performed in infant mice, and these animals were observed for 14 days after inoculation. Infectious virus or viral antigen was not detected when tissue-culture fluids from infected-mouse-brain and Py-AL/N cultures were inoculated ic into infant mice or when monolayers were examined by indirect immunofluorescence. E. Shope tested 118 viral antigens prepared from infected mouse brains with antiserum to SDA virus. cord-332233-01rdlf8l 2009 cord-333043-fe24ezt6 1977 uriae collected in the seabird colonies at Runde, Norway, two identical virus strains demonstrating no antigenic relationships to major arbovirus groups were isolated. Until then., no arbovirus isolates had been reported from this country, although ecological and cli-nicaI/epidemiological considerations (3, 24, 26) and a limited serological survey on bovine sera (28) indicated the existence of Central-European tick-borne encephalitis virus fool. uriae ticks collected at Runde in late September 1973, three virus strains have been isolated. Cells were washed with saline, virus was diluted ~enfold from 10 -1 to t0 -6 in the medium, A volume of 0.2 ml of each dilution was inoculated into three tubes and allowed to adsorb for 1 hour at room temperature before washing with saline and addition, of new medium, Culture tubes were incubated for 8 days at 37 ° C and inspected daily for a Cytopathie effect (CPE). Virus from mouse brains and cell culture demonstrated total i d e n t i t y b y these methods. cord-335424-h84jtx94 2020 cord-337464-otwps68u 2020 cord-345359-okmkgsbr 2020 cord-347039-eap592i7 2003 cord-348091-pnvn0x4q 2016 Synonym: Cell death Pathogenesis: Unregulated, energy independent, passive cell death with leakage of cytoplasm into surrounding tissue and subsequent inflammatory reaction (single cell necrosis) and/ or gene regulated, energy dependent process leading to formation of apoptotic bodies which are phagocytosed by adjacent cells (apoptosis); typically associated with cytotoxic chemotherapeutics that affect the mucosal epithelium of the tongue, esophagus and/or pharynx. In addition to the proliferative lesions of squamous cell origin, neoplasms of the bone, tooth, or adjacent soft tissues (malignant schwannoma, Zymbal''s gland tumor) may extend into the oral cavity and be associated with a gross observation at this location. Synonym: Cell death Pathogenesis: Unregulated, energy independent, passive cell death with leakage of cytoplasm into surrounding tissue and subsequent inflammatory reaction (single cell necrosis) AND/OR gene regulated, energy dependent process leading to formation of apoptotic bodies which are phagocytosed by adjacent cells (apoptosis); typically associated with cytotoxic chemotherapeutics that affect the mucosal epithelium of the nonglandular stomach. cord-350593-bvmg7f15 2012 CONCLUSIONS: MID (50) for inspired H1N1 aerosols in CD‐1 mice is between 12 and 40 TCID (50); proportionality to dose of weight loss and viral populations makes the CD‐1 mouse a useful model for measuring infectivity by inhalation. Although a few publications have documented the transmissibility of influenza A through inhalation routes (Tellier 2006 (Tellier , 2009 , few studies to date have utilized a mouse model to investigate susceptibility to and pathogenicity of measured aerosol exposures. Table 2 Results of three assays [PCR, direct fluorescent antibody assay (DFA) and CPE] from the homogenates of CD-1 murine lung tissue exposed to an aerosol generated from 1Á58 9 10 6 TCID 50 ml À1 At the 3-min exposure time, no mice were positive for influenza virus as determined by Ct value. cord-351011-v4zmksio 2020 cord-352480-1ay8y7li 2017 cord-353190-7qcoxl81 2012 This chapter covers infections of mice with the following viruses: herpesviruses, mousepox virus, murine adenoviruses, polyomaviruses, parvoviruses, lactate dehydrogenase-elevating virus, lymphocytic choriomeningitis virus, mammalian orthoreovirus serotype 3, murine hepatitis virus, murine norovirus, murine pneumonia virus, murine rotavirus, Sendai virus, and Theiler''s murine encephalomyelitis virus. These results are very difficult to summarize because the outcome of experimental infection in laboratory mice depends on various factors such as mouse strain and age, virus strain and passage history [26] , virus dose and route of inoculation [24] . Experimental infection of laboratory mice with MHV-68 is a frequently used model system for the study of human gammaherpesvirus pathogenesis, e.g. of Kaposi''s sarcoma-associated herpesvirus or Epstein-Barr virus (EBV) [62, 63] which are members of the same subfamily. Early descriptions of naturally occurring disease may have been complicated by concurrent infections such as MHV (murine hepatitis virus) or murine rotavirus A (MuRV-A)/epizootic diarrhoea of infant mice (EDIM) virus that contributed to the severity of the lesions especially in liver, pancreas, CNS and intestine. cord-353600-5wo74ms4 2020 cord-354325-r73datur 2002 Attempts to use mouse myeloma cells to create hybrids and derive human MAbs led to the loss of human chromosomes and the inability to make human Igs. 13 Unfortunately, in vitro immunization is limited by its inability to produce a secondary response and by the absence of the affinity maturation process that occurs in vivo. In these transgenic mouse models, human antibodies with high affinity to an immunized antigen are naturally selected by the murine immune system via an affinity maturation process, and thereby show increased diversity of the MAbs. Transgenic mice may be a suitable alternative to chimeric or humanized antibody production or the use of phage display systems to create less immunogenic or novel antibodies. [43] [44] [45] Humanizing Monoclonal Antibodies Rodent MAbs with excellent affinities and specificities have been generated using conventional hybridoma technology, but their use in clinical medicine is limited due to the immune responses they elicit in humans.