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

Y Shinkai, KP Lam, EM Oltz, V Stewart, M Mendelsohn… - Cell, 1992 - cell.com
Y Shinkai, KP Lam, EM Oltz, V Stewart, M Mendelsohn, J Charron, M Datta, F Young…
Cell, 1992cell.com
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 …
Summary
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.
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