Genetic and histopathological characterization of a novel arthritis model resembling rheumatoid arthritis with temporomandibular joint lesion

为建立高发生率的关节炎模型，制备回交代小鼠MRL/lpr x (MRL/lpr x C3H/lpr)F1，根据关节肿胀的宏观表现选择重度关节炎小鼠，继续进一步杂交。从F54代开始，小鼠重组基因株命名为McH-lpr/lpr-RA1 （McH/lpr-RA1）。与MRL/lpr小鼠相比，McH/lpr- ra1小鼠的关节炎发生时间更早，发病率更高，镜下表现为严重的骨破坏和主动吸收，导致强直。McH/lpr-RA1的颞下颌关节出现骨赘形成。这些结果表明，基因组重组导致关节炎病理表型的重塑。此外，我们最近发现，在两种fas缺陷小鼠的后代中，特定的F_1小鼠会自发发生关节病；MRL/lpr的突变亚株（MRL/rpl）和C3H/lpr。为明确该关节病模型独特的遗传模式，对MRL/rpl、C3H/lpr、（MRL/rpl × C3H/lpr）（MC）F_1、（C3H/lpr × MRL/rpl）（CM）F_1和MCF_2进行了选育和分析。MCF_1组男性和女性关节镜病变发生率分别为100%和19.4%。亲本株、MRL/rpl、C3H/lpr及CMF_1小鼠均无发病。MCF_1小鼠关节病变主要累及踝关节，组织病理学表现为踝关节内明显的骨骺增生，软骨细胞分化和骨化。在D7Mit68远端（60 cM）定位了MRL/rpl衍生的常染色体显性易感位点。MCF_1小鼠稳定发展为自发性踝关节强直性疾病，且雄性优势。强直的独特遗传模式可能是常染色体显性位点和y连锁位点之间的遗传相互作用。少

To develop arthritis model in higher incidence, backcross generation mice, MRL/lpr x (MRL/lpr x C3H/lpr)F1, was prepared, and the mice developing severe arthritis were selected based on macroscopic findings of joint swelling and continued further intercrosses. From generation F54, the recombinant congenic strain of mice was designated McH-lpr/lpr-RA1 (McH/lpr-RA1). Arthritis in McH/lpr-RA1 mice developed earlier and in higher incidence compared with that in MRL/lpr mice, microscopically showing severe bone destruction with active resorption, resulting in ankylosis. Moreover, temporomandibular joint of McH/lpr-RA1 showed osteophyte formation. These results indicate that genomic recombination causes the remodeling of pathological phenotypes of arthritis. In addition, we recently found the spontaneous onset of arthropathy in the particular F_1 mice descended from two Fas-deficient strains of mice ; a mutant substrain of MRL/lpr (MRL/rpl) and C3H/lpr. To clear the histopathological charact … More erization and genetic interpretation for the unique inheritance mode of disease in this arthropathy model, MRL/rpl, C3H/lpr, (MRL/rpl x C3H/lpr)(MC)F_1, (C3H/lpr x MRL/rpl)(CM)F_1 and MCF_2 were bred and were analyzed. Incidence of microscopic arthropathy in the male and female MCF_1 groups was 100% and 19.4%, respectively. No incidence was observed in the parental strains, MRL/rpl and C3H/lpr, and CMF_1 mice. In the MCF_1 mice, the arthropathy mainly affected ankle joints and was histopathologically characterized by marked entheseal proliferation with chondrocytic differentiation and ossification in the ankle joints. An MRL/rpl-derived autosomal dominant susceptibility locus to the ankylosis onset was mapped in the distal of D7Mit68 (60 cM). The MCF_1 mice stably develop spontaneous ankylosing disorders in the ankle with male-predominance. The unique inheritance mode of ankylosis is possibly interpreted by the genetic interaction between the autosomal dominant locus and a Y-linked locus. Less