Osman G E, Hannibal M C, Anderson J P, Lasky S R, Ladiges W C, Hood L
Department of Molecular Biotechnology, Box 357650, University of Washington School of Medicine, Seattle, WA 98195, USA.
Immunogenetics. 1999 Sep;49(10):851-9. doi: 10.1007/s002510050564.
Animal models of autoimmune diseases have been instrumental in advancing our understanding of autoimmunity in humans. Collagen-induced arthritis (CIA) in mice is an autoimmune disease model of rheumatoid arthritis. Susceptibility to CIA in mice is linked to genes of the major histocompatibility complex (MHC). CD4(+) T cells that express the T-cell receptor (TCR) Tcra-V11.1 and/or Tcrb-V8.2 play a key role in the pathogenesis of arthritis in the DBA/1 mouse (H2(q)). We identified an inbred mouse strain, FVB/NJ (H2(q)), that is resistant to arthritis induction and exhibits a genomic deletion of certain Tcrb-V gene segments. We report a novel polymerase chain reaction-based method for the rapid identification of new mouse strains that exhibit germline Tcrb-V gene deletions. We mapped for the first time both the 5' and 3' breakpoints of the Tcrb-V deletion in the FVB/NJ, SWR, SJL, C57L, and C57BR strains to within 1.1 kilobases. Since there is an association between a particular Tcra-V allele (Tcra-V11.1(d)) and arthritis susceptibility in H2(q) mouse strains, we examined the allelic polymorphisms of the Tcra-V11 gene subfamily members between the arthritis-susceptible DBA/1 mouse and the arthritis-resistant FVB/NJ mouse strain. The amino acid sequences of the Tcra-V11.1 alleles differ at two positions (codons 18 and 68). Therefore, the resistance of FVB/NJ mouse to arthritis induction may be due in part to Tcra-V11.1 coding sequence polymorphism and Tcrb-V8.2 gene segment deletion, as we have recently demonstrated in the case of SWR mouse strain.
自身免疫性疾病的动物模型对推动我们对人类自身免疫的理解起到了重要作用。小鼠胶原诱导性关节炎（CIA）是类风湿性关节炎的一种自身免疫性疾病模型。小鼠对CIA的易感性与主要组织相容性复合体（MHC）的基因有关。表达T细胞受体（TCR）Tcra-V11.1和/或Tcrb-V8.2的CD4(+) T细胞在DBA/1小鼠（H2(q)）关节炎的发病机制中起关键作用。我们鉴定出一种近交小鼠品系FVB/NJ（H2(q)），它对关节炎诱导具有抗性，并且某些Tcrb-V基因片段存在基因组缺失。我们报告了一种基于聚合酶链反应的新方法，用于快速鉴定表现出种系Tcrb-V基因缺失的新小鼠品系。我们首次将FVB/NJ、SWR、SJL、C57L和C57BR品系中Tcrb-V缺失的5'和3'断点定位到1.1千碱基范围内。由于在H2(q)小鼠品系中特定的Tcra-V等位基因（Tcra-V11.1(d)）与关节炎易感性之间存在关联，我们检测了关节炎易感的DBA/1小鼠和关节炎抗性的FVB/NJ小鼠品系之间Tcra-V11基因亚家族成员的等位基因多态性。Tcra-V11.1等位基因的氨基酸序列在两个位置（密码子18和68）存在差异。因此，FVB/NJ小鼠对关节炎诱导的抗性可能部分归因于Tcra-V11.1编码序列多态性和Tcrb-V8.2基因片段缺失，正如我们最近在SWR小鼠品系中所证明的那样。
