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- Title
Characterization of immunoglobulin heavy chain knockout rats.
- Authors
Ménoret, Séverine; Iscache, Anne-L.; Tesson, Laurent; Rémy, Séverine; Usal, Claire; Osborn, Michel J.; Cost, Gregory J.; Brüggemann, Marianne; Buelow, Roland; Anegon, Ignacio
- Abstract
The rat is a species frequently used in immunological studies but, until now, there were no models with introduced gene-specific mutations. In a recent study, we described for the first time the generation of novel rat lines with targeted mutations using zinc-finger nucleases. In this study, we compare immune development in two Ig heavy-chain KO lines; one with truncated Cμ and a new line with removed JH segments. Rats homozygous for IgM mutation generate truncated Cμ mRNA with a de novo stop codon and no Cγ mRNA. JH-deletion rats showed undetectable mRNA for all H-chain transcripts. No serum IgM, IgG, IgA and IgE were detected in these rat lines. In both lines, lymphoid B-cell numbers were reduced >95% versus WT animals. In rats homozygous for IgM mutation, no Ab-mediated hyperacute allograft rejection was encountered. Similarities in B-cell differentiation seen in Ig KO rats and ES cell-derived Ig KO mice are discussed. These Ig and B-cell-deficient rats obtained using zinc-finger nucleases-technology should be useful as biomedical research models and a powerful platform for transgenic animals expressing a human Ab repertoire.
- Publication
European Journal of Immunology, 2010, Vol 40, Issue 10, p2932
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201040939