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Somatic Recombination of Heavy Chain Variable Region Transgenes with the Endogenous Immunoglobulin Heavy Chain Locus in Mice

Transgenic lines of mice were derived by using plasmid constructs containing DNA encoding an antibody heavy chain variable-diversity-joining region (VH-D-JH) and various amounts of 5' and 3' flanking DNA but lacking any repetitive isotype switch (S) or constant (C) region DNA. Unexpectedly...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1992-11, Vol.89 (21), p.10321-10325
Main Authors: Giusti, Angela M., Coffee, Richard, Manser, Tim
Format: Article
Language:English
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Summary:Transgenic lines of mice were derived by using plasmid constructs containing DNA encoding an antibody heavy chain variable-diversity-joining region (VH-D-JH) and various amounts of 5' and 3' flanking DNA but lacking any repetitive isotype switch (S) or constant (C) region DNA. Unexpectedly, many of the antibody VHregions expressed by B-cell hybridomas generated from immunized transgenic mice were found to be of transgenic origin. Further analyses showed that somatic events had generated hybrid genomic loci in the mice containing the transgenic VH-D-JHgene and plasmid sequences 5' of endogenous heavy chain C region genes. Thus, VH-D-JHtransgenes lacking S and C region DNA can recombine with endogenous Igh DNA, leading to the expression of transgene-encoded antibody.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.89.21.10321