Previously, we described a @entity803 -based autoregulatory system for inducible gene expression in @entity1 cells and @entity19 [Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 6522]. We have tested the ability of this system to drive functional expression in vivo of the V(D)J recombination activating genes, @entity5350 and @entity6233 . In induced @entity19 , transgenic @entity5350 and @entity6233 mRNA is observed in thymus and spleen, and expression of both transgenes on the @entity5350 or @entity6233 knockout backgrounds allows partial, inducible, lymphocyte reconstitution. In thymus and peripheral lymphoid organs of reconstituted animals, cells expressing @entity1961 and/or CD8 on their surface, also express @entity5168 and TCR beta chain. In these animals, V(D)J rearrangements are detected in thymus, lymph nodes, and spleen at the @entity9751 locus, and in thymus and lymph nodes at the @entity55171 locus. At the TRA locus, broken ends at V(D)J recombination signals are detected only in thymus, as are reciprocal signal joint products derived from deletional rearrangement. T cell reconstitution occurs in these animals whether they are induced in utero during development, or shortly after birth. A low level of B cell reconstitution is also observed. B220+IgM+ cells are observed in spleen only in induced animals, and rearrangements at @entity7528 and @entity11741 loci are detected in bone marrow and spleen. Broken signal ends at the @entity11741 locus, are not detected in peripheral lymphoid organs. Inducible reconstitution of normal levels of serum immunoglobulin, including heavy chain class switch isotype variants is also observed in these animals. Further, these transgenes do not appear to interfere with lymphocyte development mediated by functionally rearranged @entity9751 chain or @entity7528 chain transgenes in RAG-deficient animals. These @entity19 provide a unique system for the inducible activation of V(D)J recombination and the development of primary lymphocytes.

Partial reconstitution of V(D)J rearrangement and lymphocyte development in RAG-deficient XXXX expressing inducible, @entity803 -regulated RAG transgenes.

@entity1 :: ('9606', 'Species') :: ['mammalian'] @entity11741 :: ('243469(Tax:10090)', 'Gene') :: ['IGK'] @entity6233 :: ('19374(Tax:10090)', 'Gene') :: ['RAG2'] @entity19 :: ('10090', 'Species') :: ['mice', 'transgenic mice'] @entity5168 :: ('12501(Tax:10090)', 'Gene') :: ['CD3'] @entity1961 :: ('12504(Tax:10090)', 'Gene') :: ['CD4'] @entity7528 :: ('111507(Tax:10090)', 'Gene') :: ['IGH'] @entity5350 :: ('19373(Tax:10090)', 'Gene') :: ['RAG1'] @entity55171 :: ('109869(Tax:10090)', 'Gene') :: ['TRD'] @entity803 :: ('MESH:D013752', 'Chemical') :: ['tetracycline'] @entity9751 :: ('56321(Tax:10090)', 'Gene') :: ['TRB']
@entity19 :: (10090,Species) :: ['mice']
