Abstract
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
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Carrier Proteins / metabolism
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Cell Differentiation
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DNA-Binding Proteins*
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Gene Expression Regulation
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Homeodomain Proteins*
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Hyaluronan Receptors
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Immunity, Cellular
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Immunologic Deficiency Syndromes / genetics
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Lymphoid Tissue / cytology
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Lymphoid Tissue / immunology
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Mice
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Mice, Transgenic
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Phenotype
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Promoter Regions, Genetic
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Proteins / genetics*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Antigen, T-Cell / metabolism
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Receptors, Cell Surface / metabolism
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Receptors, Lymphocyte Homing / metabolism
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology*
Substances
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Carrier Proteins
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DNA-Binding Proteins
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Homeodomain Proteins
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Hyaluronan Receptors
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Proteins
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RNA, Messenger
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Rag2 protein, mouse
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Receptors, Antigen, T-Cell
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Receptors, Cell Surface
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Receptors, Lymphocyte Homing
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V(D)J recombination activating protein 2
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RAG-1 protein