Experiment
Recombinant inbred (RI) strain BXSB/MpJScr-long-lived displays delayed development of systemic lupus erythematosus (SLE). Fifty-percent of males from BXSB/MpJScr-ll survive past 21 months of age and display decreased levels of antinuclear antibodies. This RI strain is a substrain of BXSB/MpJ derived from progenitor strains C57BL/6 and SB/Le.
A screen of 13,374 SNPs revealed genetic differences between BXSB/MpJ and BXSB/MpJScr-ll on chromosomes 3, 5, 6, 9, 11, 12, and 13. It is believed a recessive SB/Le-derived resistance QTL is located in one or more of these intervals. Bsx6 is a previously identified QTL on mouse Chromosome 13 corresponding to an interval between D13Mit64 (30 cM) and D13Mit233 (45 cM) that is genetically distinct between BXSB/MpJScr-ll and BXSB/MpJ. However, based on the similar autoantibody profiles between BXSB/MpJScr-ll and BXSB/MpJ the authors believe this locus is intact. Previously identified SLE susceptibility loci Sles3 (78.5 cM on chr 3) and Sles4 (9.1 Mb on chr 9) map to C57BL/6-derived regions on BXSB/MpJScr-ll. These 2 loci could perhaps act as C57BL/6-derived suppressors of SLE.
Previously identified SLE susceptibility loci Sle10 (formerly Bxs3, chr 1) and Yaa4 (formerly Bxs4, chr 1) were identical between BXSB/MpJ andBXSB/MpJScr-ll. Therefore, these loci cannot explain the increased SLE susceptibility in BXSB/MpJScr-ll.
A SLE susceptibility locus on the Y chromosome, Yaa, was examined. This locus is presumed to be a duplication of a region containing Tlr7. When probed for Tlr7 sequences it was observed that BXSB/MpJScr-ll mice carried the same copy number as BXSB/MpJ but significantly higher copy numbers compared to C57BL/10ScSn mice.
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