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Publication : Functional transplant of megabase human immunoglobulin loci recapitulates human antibody response in mice.

First Author  Mendez MJ Year  1997
Journal  Nat Genet Volume  15
Issue  2 Pages  146-56
PubMed ID  9020839 Mgi Jnum  J:70620
Mgi Id  MGI:2137848 Doi  10.1038/ng0297-146
Citation  Mendez MJ, et al. (1997) Functional transplant of megabase human immunoglobulin loci recapitulates human antibody response in mice. Nat Genet 15(2):146-56
abstractText  We constructed two megabase-sized YACs containing large contiguous fragments of the human heavy and kappa (kappa) light chain immunoglobulin (Ig) loci in nearly germline configuration, including approximately 66 VH and 32 V kappa genes. We introduced these YACs into Ig-inactivated mice and observed human antibody production which closely resembled that seen in humans in all respects, including gene rearrangement, assembly, and repertoire. Diverse Ig gene usage together with somatic hypermutation enables the mice to generate high affinity fully human antibodies to multiple antigens, including human proteins. Our results underscore the importance of the large Ig fragments with multiple V genes for restoration of a normal humoral immune response. These mice are likely to be a valuable tool for the generation of therapeutic antibodies.
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