RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement.
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.
Shinkai
Y
Y
Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Rathbun
G
G
Lam
K P
KP
Oltz
E M
EM
Stewart
V
V
Mendelsohn
M
M
Charron
J
J
Datta
M
M
Young
F
F
Stall
A M
AM
D000818:Animals; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000737:chemistry*; D001483:Base Sequence; D004254:DNA Nucleotidyltransferases / Q000032:analysis*; D004268:DNA-Binding Proteins; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics*; D019426:Integrases; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010641:Phenotype; D011506:Proteins / Q000032:analysis / Q000235:genetics*; D045522:Recombinases; D013601:T-Lymphocytes / Q000737:chemistry*
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D011506:Proteins; C499308:Rag2 protein, mouse; D045522:Recombinases; C064655:V(D)J recombination activating protein 2; D004254:DNA Nucleotidyltransferases; D019426:Integrases; C115006:integron integrase IntI1