Studies on background genes aggravating lpr^<cg>-induced nephritis and complementation between lpr^<cg> and gld genes

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Linkage tests were conducted using the intersubspecific backcross of (CBA-lpr^<cg> x MOL-MIT)F_1 x CBA-lpr^<cg> and led to the conclusion that the lpr^<cg> gene locates between Ly-44 and Tdt on chromosome 19 at the distances : centromere-Ly-44 -(17.0 cM)-lpr^<cg>-(5.3 cM)-Tdt-telomere.Both homozygous and heterozygous lpr^<cg> gene induced more severe autoimmune syndromes, nephritis and vasculitis on the MRL than the CBA background. To analyze the effects of background genes, backcross offspring were examined from the interspecific cross of (MRL-lpr x CAST/Ei)F_1 x MRL-lpr. The profound effects of background genes on the extent of nephritis, lymphadenopathy and anti-DNA antibody were demonstrated. Of major note, this study suggested the identification of chromosomal positions for genes that modify nephritis. Analysis of the backcross mice for markers covering most of the mouse genome suggest that over 50% of the variance in renal disease is attributable to quantitative trait loci on mouse chromosomes 7 and 12. These loci may also participate in aggravation of lpr^<cg>-induced nephritis.Simultaneous bone marrow (BM) and lymph node (LN) transplantation into (CBA x C3H)F_1 (F_1) mice was performed in various genotype combinations. Grafted C3H-lpr/lpr and CBA-lpr^<cg> LN swelled but +/+ and C3H-gld/gld LN strophied in recipients of lpr/lpr or lpr^<cg>/lpr^<cg> BM.All LN of these genotypes swelled in recipients of gld/gld BM.Thus, lpr and lpr^<cg> are phenotypically different from gld in the interaction of BM-derived double negative (DN) T cells and +/+ LN.Lymphadenopathy induced by the cooperation between lpr^<cg> and gld was confirmed to be lpr but not of gld phenotype by a similar method.