A regulatory role for recombinase activating genes, RAG-1 and RAG-2, in T cell development.
RAG-1 and RAG-2 are developmentally regulated genes that are essential for the assembly of antigen receptors in lymphoid cells. Here we describe transgenic mice that carry RAG-1 and RAG-2 under the control of the proximal lck promoter. Persistent expression of RAG-1 and RAG-2 was associated with incomplete thymopoiesis and profoundly compromised cellular immunity. In addition, RAG transgenic mice rapidly developed lymphadenopathy, splenomegaly, and lymphocytic perivascular infiltrates. These effects required both RAG-1 and RAG-2, since mice that carried either gene exclusively were indistinguishable from wild-type controls. We propose that in addition to a previously documented role in V(D)J recombination, RAG-1 and RAG-2 expression must be properly regulated for completion of normal T cell development
Wayne
J
J
Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021.
Suh
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Misulovin
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Sokol
K A
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Inaba
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Nussenzweig
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MC
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins; D018960:Hyaluronan Receptors; D007111:Immunity, Cellular; D007153:Immunologic Deficiency Syndromes / Q000235:genetics; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D018960:Hyaluronan Receptors; D011506:Proteins; D012333:RNA, Messenger; C499308:Rag2 protein, mouse; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein