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 desc ribe transgenic mice that carry RAG-1 and RAG-2 under the control of t he proximal Ick promoter. Persistent expression of RAG-1 and RAG-2 was associated with incomplete thymopoiesis and profoundly compromised ce llular immunity. In addition, RAG transgenic mice rapidly developed ly mphadenopathy, 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.