Nose M, Terada M, Nishihara M, Kamogawa J, Miyazaki T, Mori S, Nishimura M, Wang Y, Kamoto T, Hiai H
Department of Pathology, Ehime University School of Medicine, Shigenobu, Japan.
Int J Cardiol. 1998 Oct 1;66 Suppl 1:S37-41; discussion S43. doi: 10.1016/s0167-5273(98)00146-6.
Autoimmune diseases show complex pathological manifestations, which frequently involve systemic vasculitis. This complication is understood to be a manifestation of advanced disease, or to represent distinct entities, restricted by genetic and/or environmental factors. An MRL/Mp strain of mice bearing the Fas deletion mutant gene, lpr (MRL/lpr), spontaneously develop systemic vasculitis coincidentally with glomerulonephritis, arthritis and sialoadenitis, but a C3H/HeJ-lpr/lpr (C3H/lpr) strain does not. Thus, this is a suitable model for analyzing the genetic basis of vasculitis in autoimmune diseases. To genetically dissect these complex pathological manifestations, a linkage analysis of each lesion with polymorphic microsatellite markers was performed by using MRL/lpr x (MRL/lpr x C3H/lpr)F1 backcross mice. Vasculitis-susceptible gene loci were mapped on chromosomes 3 and 4, which were not associated with glomerulonephritis, arthritis and sialoadenitis. These results indicate that systemic vasculitis in MRL/lpr mice may be under the control of host genes which are different from those for other autoimmune diseases.
自身免疫性疾病表现出复杂的病理表现，常累及系统性血管炎。这种并发症被认为是疾病进展的表现，或者代表受遗传和/或环境因素限制的不同实体。携带Fas缺失突变基因lpr的MRL/Mp品系小鼠（MRL/lpr）会自发出现系统性血管炎，同时伴有肾小球肾炎、关节炎和涎腺炎，但C3H/HeJ-lpr/lpr（C3H/lpr）品系小鼠则不会。因此，这是分析自身免疫性疾病中血管炎遗传基础的合适模型。为了从基因层面剖析这些复杂的病理表现，利用MRL/lpr×（MRL/lpr×C3H/lpr）F1回交小鼠，对每个病变与多态性微卫星标记进行了连锁分析。血管炎易感基因位点定位于3号和4号染色体上，这些位点与肾小球肾炎、关节炎和涎腺炎无关。这些结果表明，MRL/lpr小鼠的系统性血管炎可能受宿主基因控制，这些基因与其他自身免疫性疾病的基因不同。
