Genetic dissection of vasculitis in MRL/lpr lupus mice: a novel susceptibility locus involving the CD72c allele
✍ Scribed by Wei-Min Qu; Tatsuhiko Miyazaki; Miho Terada; Ling-Min Lu; Miyuki Nishihara; Akihiro Yamada; Shiro Mori; Yusuke Nakamura; Hideaki Ogasawara; Chie Yazawa; Syuichi Nakatsuru; Masato Nose
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 185 KB
- Volume
- 30
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
An MRL/MpJ strain of mice bearing the Fas deletion mutant gene, lpr (MRL/lpr), composed of genomes derived from LG/J, AKR/J, C3H/Di and C57BL/6J mice, develops systemic vasculitis coincidentally with other collagen diseases, but a C3H/HeJ-lpr/lpr (C3H/lpr) strain does not. In a genome-wide screening of the MRL background genes mediating susceptibility to collagen diseases using N2 progeny mice MRL/lpr × (MRL/lpr × C3H/lpr)F1, we previously found that each collagen disease is controlled by a different set of genes. To clarify the candidate genes for vasculitis, we extended the linkage analysis of renal vasculitis to a larger number of N2 mice and to F2 intercross mice. Two distinct recessive susceptibility loci for vasculitis were mapped on chromosome (Chr) 4 at D4Mit89 and D4Mit147 in both progenies. The former was a novel locus for lupus phenotypes, which involved the MRL allele CD72 c in contrast to the C3H allele CD72 b . The one on Chr 3 was a recessive locus which had an inhibitory effect on vasculitis. From their composition these loci seemed to be derived from AKR/J (for one) and LG/J (for another two) strains, and appeared to act in an additive manner on the development of vasculitis, indicating that vasculitis in MRL/lpr mice is inherited in a polygenic manner.