Multiplex inheritance of component phenotypes in a murine model of lupus

We analyzed the linkage of GN and a wide spectrum of serological phenotypes associated with systemic lupus erythematosus in a (NZM2410 x C57BL/6)F-2 c ross. Some phenotypes, such as glomerulonephritis (GN) and anti-chromatin I gG antibody production, were more penetrant in females, but others, such as anti-dsDNA antibody production, did not show a gender bias. These results suggest that gender bias affects only a subset of SLE-component phenotypes, and that NZM2410 can be used to dissect the genetic basis of this phenomen on. Genome scanning linked six chromosomal intervals with the expression of one or more component phenotypes. These loci included two Sie loci previou sly identified in an (NZM2410 x B6)F-1 x NZM2410 backcross, loci identified by others in the NZB/W model. Our analysis also suggested two new interval s on chromosomes (Chrs.) 10 and 11. Detailed analysis of the segregation of different phenotypes within these intervals suggests that they encompass m ore than one susceptibility locus. This clustering has been a common findin g in several murine polygenic traits. Each of NZM2410 susceptibility loci c an be aligned with a specific genetic pathways contributing to SLE; pathoge nesis on the basis of the spectrum of component phenotypes expressed.