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• W2798889337 abstract "Randall S. Johnson,7 Karl Herrup,* Susumu Tonegawa, * and Virginia E. PapaioannouO *Howard Hughes Medical Institute at the Center for Cancer Research and Department of Biology Massachusetts Institute of Technology Cambridge, Massachusetts 02139 tDana-Farber Cancer Institute and Department of Biological Chemistry and Molecular Pharmacology Harvard Medical School Boston, Massachusetts 02115 $Developmental Neurobiology Shriver Center for Mental Retardation 200 Trapelo Road Waltham, Massachusetts 02254 SDepartment of Pathology Tufts University School of Medicine and Veterinary Medicine Boston, Massachusetts 02111 Summary The V(D)J recombination activation gene RAG-1 was isolated on the basis of its ability to activate V(D)J re- combination on an artificial substrate in fibroblasts. This property and the expression pattern in tissues and cell lines indicate that RAG-1 eitheractivatesorcata- lyres the V(D)J recombination reaction of immuno- globulin and T cell receptor genes. We here describe the introduction of a mutation in RAG-1 into the germ- line of mice via gene targeting in embryonic stem cells. RAG-l-deficient mice have small lymphoid organs that do not contain mature Band 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 re- combination. 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 neu- roanatomical or behavioral abnormalities have been found in the RAG-l-deficient mice. Introduction The generation of antibody and Tcell receptor (TCR) diver- sity is mediated to a large extent by the somatic DNA rearrangement known as V(D)J recombination, which joins variable (V), diversity (D), and joining (J) gene seg- ments (Tonegawa, 1983). The genes for the antigen recep- tors are assembled through this process exclusively in lymphocytes. V(D)J recombination occurs at seven differ- ent loci: the immunoglobulin (lg) heavy chain," @default.
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• W2798889337 date "1992-01-01" @default.
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• W2798889337 title "RAG-l-Deficient Mice Have No Mature 8 and T Lymphocytes" @default.
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