Qu W M, Miyazaki T, Terada M, Lu L M, Nishihara M, Yamada A, Mori S, Nakamura Y, Ogasawara H, Yazawa C, Nakatsuru S, Nose M
Department of Pathology, Ehime University School of Medicine, Japan.
Eur J Immunol. 2000 Jul;30(7):2027-37. doi: 10.1002/1521-4141(200007)30:7<2027::AID-IMMU2027>3.0.CO;2-S.
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 x (MRL/lpr x 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.
携带Fas缺失突变基因lpr的MRL/MpJ品系小鼠（MRL/lpr），其基因组源自LG/J、AKR/J、C3H/Di和C57BL/6J小鼠，会与其他胶原病同时发生系统性血管炎，但C3H/HeJ-lpr/lpr（C3H/lpr）品系小鼠则不会。在使用N2子代小鼠MRL/lpr×（MRL/lpr×C3H/lpr）F1对介导胶原病易感性的MRL背景基因进行全基因组筛选时，我们先前发现每种胶原病由不同的基因集控制。为了明确血管炎的候选基因，我们将肾血管炎的连锁分析扩展到更多的N2小鼠和F2杂交小鼠。在两个子代中，两个不同的血管炎隐性易感位点被定位在第4号染色体（Chr）上的D4Mit89和D4Mit147处。前者是狼疮表型的一个新位点，与C3H等位基因CD72(b)相比，它涉及MRL等位基因CD72(c)。位于Chr 3上的那个是对血管炎有抑制作用的隐性位点。从它们的组成来看，这些位点似乎分别源自AKR/J品系（其中一个）和LG/J品系（另外两个），并且似乎以累加方式作用于血管炎的发生发展，这表明MRL/lpr小鼠的血管炎是以多基因方式遗传的。
