RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement

Yoichi Shinkai, 0Gary Rathbun, Kong Peng Lam, Eugene M. Oltz, Valerie Stewart, Monica Mendelsohn, Jean Charron, Milton Datta, Faith Young, Alan M. Stall, Frederick W. Alt

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2080 Scopus citations


We have generated mice that carry a germline mutation in which a large portion of the RAG-2 coding region is deleted. Homozygous mutants are viable but fail to produce mature B or T lymphocytes. Very immature lymphoid cells were present in primary lymphoid organs of mutant animals as defined by surface marker analyses and Abelson murine leukemia virus (A-MuLV) transformation assays. However, these cells did not rearrange their immunoglobulin or T cell receptor loci. Lack of V(D)J recombination activity in mutant pre-B cell lines could be restored by introduction of a functional RAG-2 expression vector. Therefore, loss of RAG-2 function in vivo results in total inability to initiate V(D)J rearrangement, leading to a novel severe combined immune deficient (SCID) phenotype. Because the SCID phenotype was the only obvious abnormality detected in RAG-2 mutant mice, RAG-2 function and V(D)J recombinase activity, per se, are not required for development of cells other than lymphocytes.

Original languageEnglish
Pages (from-to)855-867
Number of pages13
Issue number5
StatePublished - Mar 6 1992

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