Mori Shiro, Tanda Naoko, Ito Mitsuko R, Oishi Hisashi, Tsubaki Takahito, Komori Hiroaki, Zhang Ming-Cai, Ono Masao, Nishimura Masahiko, Nose Masato
Tohoku University Graduate School of Dentistry, Sendai, Japan.
Pathol Int. 2008 Jul;58(7):407-14. doi: 10.1111/j.1440-1827.2008.02245.x.
Based on the hypothesis that the complex pathological and immunological manifestations of rheumatoid arthritis (RA) and the related diseases are under the control of multiple gene loci with allelic polymorphism, a recombinant congenic mouse strain was prepared between an MRL/Mp-lpr/lpr (MRL/lpr) strain, which develops arthritis resembling RA, and a non-arthritic strain C3H/HeJ-lpr/lpr (C3H/lpr). In MRL/lpr x (MRL/lpr x C3H/lpr) F1 mice, the mice developing severe arthritis were selected based on joint swelling to further continue intercrosses, and then an McH-lpr/lpr-RA1 (McH/lpr-RA1) strain was established and its histopathological phenotypes of joints and autoimmune traits were analyzed. Arthritis in McH/lpr-RA1 mice developed at a higher incidence by 20 weeks of age, compared with that in the MRL/lpr mice, who had severe synovitis (ankle, 60.3%; knee, 65.1%), and also fibrous and fibrocartilaginous lesions of articular ligamenta resembling enthesopathy (ankle, 79.4%; knee, 38.1%), resulting in ankylosis. The lymphoproliferative disorder was less, and serum levels of IgG and IgG autoantibodies including anti-dsDNA and rheumatoid factor were lower than those of both MRL/lpr and C3H/lpr strains. McH/lpr-RA1 mice may provide a new insight into the study of RA regarding the common genomic spectrum of seronegative RA and enthesopathy.
基于类风湿关节炎(RA)及相关疾病复杂的病理和免疫表现受多个具有等位基因多态性的基因位点控制这一假说,在表现出类似RA关节炎的MRL/Mp-lpr/lpr(MRL/lpr)品系与非关节炎品系C3H/HeJ-lpr/lpr(C3H/lpr)之间培育了一个重组近交系小鼠品系。在MRL/lpr×(MRL/lpr×C3H/lpr)F1代小鼠中,根据关节肿胀情况挑选出发生严重关节炎的小鼠进一步进行杂交,随后建立了McH-lpr/lpr-RA1(McH/lpr-RA1)品系,并分析了其关节的组织病理学表型和自身免疫特征。与患有严重滑膜炎的MRL/lpr小鼠相比,McH/lpr-RA1小鼠在20周龄时关节炎的发病率更高(踝关节滑膜炎,MRL/lpr小鼠为60.3%,McH/lpr-RA1小鼠为79.4%;膝关节滑膜炎,MRL/lpr小鼠为65.1%,McH/lpr-RA1小鼠为38.1%),同时还出现了类似附着点病的关节韧带纤维性和纤维软骨性病变(踝关节,MRL/lpr小鼠为79.4%,McH/lpr-RA1小鼠为38.1%),导致关节强直。McH/lpr-RA1小鼠的淋巴细胞增殖性疾病较轻,血清IgG及包括抗双链DNA和类风湿因子在内的IgG自身抗体水平均低于MRL/lpr和C3H/lpr两个品系。McH/lpr-RA1小鼠可能为血清阴性RA和附着点病的共同基因组谱研究提供新的视角。