Candidate Genes for BXSB Lupus

系统性红斑狼疮或狼疮是一种多基因自身免疫性疾病，其特征是高水平的 抗核自身抗体和几种涉及B细胞的细胞异常。骨髓细胞和其他 血统狼疮的遗传基础仍有待解决。虽然几个人的大致位置 已经在许多不同的模型中阐明了鼠狼疮中的疾病易感性基因座， 在已鉴定的基因座内的罪魁祸首基因仍然难以捉摸。特别地，这对于BXSB菌株是真实的， 会自发地发展成狼疮我们最近发现了2个潜在的候选基因， 作为狼疮的罪魁祸首基因，基于表达差异，有趣的序列 多态性和表现出的功能差异。这项提案的目的是测试 这两种分子作为BXSB狼疮的潜在罪魁祸首基因，并确定这些基因如何可能 影响B细胞和骨髓细胞的功能，使用体外和体内方法。此外，我们将 评估狼疮中SDF 1/CXCR 4活性升高的起源和致病作用。鉴于 目前对狼疮的遗传学知之甚少，也不知道为什么B细胞和髓样细胞是 由于狼疮的过度活跃，拟议中的研究可以大大提高我们对这种疾病的理解。获得了 在进行更有针对性的治疗之前， 可以为这种疾病制定策略。

Systemic lupus erythematosus or lupus is a polygenic autoimmune disease characterized by high levels of anti-nuclear autoantibodies, and several cellular abnormalities involving B-cells. myeloid cells and other lineages. The genetic basis of lupus remains to be solved. Although the approximate positions of several disease susceptibility loci in murine lupus have been elucidated in many different models, the identity of the culprit genes within the identified loci remain elusive. In particular, this is true of the BXSB strain that develops lupus spontaneously. We have recently identified 2 potential candidate genes that appear attractive as culprit genes for lupus in this model, based on expression differences, intriguing sequence polymorphisms and demonstrated functional differences. The goal of this proposal is to test the candidacy of these 2 molecules as potential culprit genes for BXSB lupus, and to ascertain how these genes might influence the function of B-cells and myeloid cells, using in vitro and in vivo approaches. In addition, we will assess the origins and pathogenic contributions of heightened SDF1/CXCR4 activity in lupus. Given that very little is currently known about the genetics of lupus, or about why B-cells and myeloid cells are hyperactive in lupus, the proposed studies could greatly boost our understanding of this disease. Gaining a clear understanding of the genetic and molecular basis of lupus is essential before more targeted therapeutic strategies can be devised for this disease.