RAG-1-deficient mice have no mature B and T lymphocytes.
The V(D)J recombination activation gene RAG-1 was isolated on the basis of its ability to activate V(D)J recombination on an artificial substrate in fibroblasts. This property and the expression pattern in tissues and cell lines indicate that RAG-1 either activates or catalyzes the V(D)J recombination reaction of immunoglobulin and T cell receptor genes. We here describe the introduction of a mutation in RAG-1 into the germline of mice via gene targeting in embryonic stem cells. RAG-1-deficient mice have small lymphoid organs that do not contain mature B and T lymphocytes. The arrest of B and T cell differentiation occurs at an early stage and correlates with the inability to perform V(D)J recombination. The immune system of the RAG-1 mutant mice can be described as that of nonleaky scid mice. Although RAG-1 expression has been reported in the central nervous system of the mouse, no obvious neuroanatomical or behavioral abnormalities have been found in the RAG-1-deficient mice.
Mombaerts
P
P
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139.
Iacomini
J
J
Johnson
R S
RS
Herrup
K
K
Tonegawa
S
S
Papaioannou
V E
VE
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D001483:Base Sequence; D001854:Bone Marrow Cells; D001921:Brain / Q000033:anatomy & histology; D002454:Cell Differentiation / Q000235:genetics; D002461:Cell Line, Transformed; D015321:Gene Rearrangement / Q000235:genetics; D015329:Gene Rearrangement, T-Lymphocyte; D018398:Homeodomain Proteins; D051379:Mice; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology
D018398:Homeodomain Proteins; D011506:Proteins; C064658:RAG-1 protein