GENETICS OF ARTHRITIS IN MRL/1PR MICE AND IN HUMAN RHEUMATOID ARTHRITIS

MRL/MPJ-LPR(MRL-LPR)小鼠发生自发性炎症 由于lpr，这种滑膜炎需要来自mrl株的基因。 由于LPR基因，包括C57BL/6J-LPR(B6-LPR)、AKR/J-LPR和 不是明显的关节炎。利用MRL-1杂交组合的初步研究 MRL-LPR和B6-LPR小鼠的杂交表明 半显式。为了确定基因的数量，染色体 关节炎易感基因(S)的染色体定位和测定 滑膜炎与功能和血清学异常的关系， 异常，我们将分析回交和/或F2杂交利用 BL/6-LPR亲本菌株。这些动物后肢膝盖的组织学 这些小鼠的膝盖将被评分，结果与 类风湿因子、抗DNA抗体和包括IgG3在内的Ig水平。脱氧核糖核酸 包括lgG3。将对每个后代的DNA进行检测 以大约15%摩根的间隔贯穿小鼠基因组。 摩根区间。检测到的微卫星多态 并将使用限制片段长度变体来准确地定义 用于准确定义单倍型。影响基因座的分离 使用设计用于分析复杂结构的计算机程序来确定 分析复杂的遗传病。因为老鼠和人类的基因组 在进化过程中保存的多个染色体片段，这些 进化，这些研究有可能识别假定的遗传 人类炎症性关节病的遗传和发病机制。 关节疗法。因此，拟议的研究可能会提示候选基因 对小鼠和人类的疾病发展都至关重要。作为以下内容的一部分 作为这一努力的一部分，患有类风湿性关节炎的人类家庭也将 确定疾病是否与候选基因座分离，包括 包括MRL研究提出的建议。我们将使用受影响的 这并不是以继承模式为前提的。拟议的研究包括 拟议的研究有可能确定非主要的 在炎症性关节病的发病机制中起重要作用。 炎性关节病。

The MRL/MpJ-lpr (MRL-lpr) mouse develops spontaneous inflammatory Genes from the MRL strain are necessary for this synovitis since lpr since lpr congenics, including C57BL/6J-lpr (B6-lpr), AKR/J-lpr and not manifest arthritis. Preliminary studies using F1 crosses between MRL- crosses between MRL-lpr and B6-lpr mice indicate that the inheritance of semidominant. In order to identify the number of genes, the chromosomal chromosomal location of the arthritis susceptibility gene(s) and determine relationship between synovitis and functional and serologic abnormalities, abnormalities, we will analyze backcross and/or F2 intercrosses utilizing BL/6-lpr parental strains. The histology of the hind limb knees of these knees of these mice will be scored and the results correlated with rheumatoid factor, anti-DNA antibodies, and Ig levels including IgG3. DNA including lgG3. DNA from each of the progeny will be examined for throughout the mouse genome at approximately 15 centi-Morgan intervals. Morgan intervals. Microsatellite polymorphisms that are detected by and restriction fragment length variants will be used to accurately define used to accurately define haplotypes. The segregation of loci that affect determined using computer programs that are designed to analyze complex analyze complex genetic diseases. Since the mouse and human genomes are multiple chromosome segments that have been conserved over evolution, these evolution, these studies have the potential to identify putative genetic the inheritance and pathogenesis of human inflammatory arthropathies. arthropathies. Therefore the proposed studies may suggest candidate genes critical to the development of disease in both mice and humans. As part of As part of this effort, human families with rheumatoid arthritis will also to determine whether disease segregates with candidate loci including those including those suggested by the MRL study. We will use an affected that does not presuppose a mode of inheritance. The proposed studies have proposed studies have the potential to identify non-major important in the pathogenesis of inflammatory arthropathy. inflammatory arthropathy.