id author title date pages extension mime words sentences flesch summary cache txt cord-313506-6bb4q7nv Sano, Akiko Physiological Level Production of Antigen-Specific Human Immunoglobulin in Cloned Transchromosomic Cattle 2013-10-24 .txt text/plain 6695 313 54 We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH) and kappa-chain (hIGK) germline loci (named as κHAC) are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO). Therefore, in an effort to improve B cell development and hIgG production in Tc cattle, we sought to enhance pre-BCR function by engineering a new HAC into which, in addition to the hIGH, hIGK and hIGL chromosome loci that carry the entire human immunoglobulin gene repertoire, the human VpreB (hVPREB1) and λ5 (hIGLL1) genomic loci from human chromosome 22 (hChr22) was incorporated, and part of CH and TM domains, CH2-TM, of hIGHM gene, was replaced by the corresponding bovine gene sequence (bovinization of the CH2-TM domains of hIGHM). doi: 10.1371/journal.pone.0078119.g002 DT40 colonies were screened with genomic PCR (data not shown) for the correctly modified hChr2, and clone K53 was identified and selected for the final HAC construction ( Figure 5 ). ./cache/cord-313506-6bb4q7nv.txt ./txt/cord-313506-6bb4q7nv.txt