THE YAA MUTATION INDUCES THE DEVELOPMENT OF AUTOIMMUNITY IN MICE HETEROZYGOUS FOR THE GLD (GENERALIZED-LYMPHADENOPATHY-DISEASE) MUTATION

Mice homozygous for either the generalized lymphoproliferative disease (gld) or the lymphoproliferation (lpr) nonallelic mutations develop s imilar syndromes combining systemic autoimmunity and lymphoproliferati ve disease. Though essentially recessive, the lpr and gld mutations ma y be expressed in the heterozygous state: [lpr/+] mice displayed a mil d ''lpr-like'' autoimmunity, and the [lpr(rg)/+ gld/+] mice developed a ''gld-like'' disorder, showing interactions of the gld gene product with the nonallelic lpr(rg) product. The Y-chromosome-linked autoimmun e accelerator (Yaa) mutation being an autoimmunity accelerator, its as sociation with an heterozygous gld gene might also bring a gld-like sy ndrome. The [gld/+ Yaa] mice were shown here to develop autoimmunity a nd splenomegaly like [gld/gld] mice, but without their typical lymphad enopathy. Furthermore, the [gld/+ Yaa] splenomegaly was not due to the expansion of the unusual Thyl(+)B220(+) T-cell subset typical of the gld syndrome, but rather to a polyclonal expansion of the major lympho id cell subsets. Thus, the syndrome shown by [gld/+ Yaa] mice was not a gld-like syndrome. This suggests that the interactions of the gld ge ne product with the Yaa product and with the lpr(rg) product must be d ifferent. (C) 1994 Academic Press, Inc.