Candidate Genes for BXSB Lupus

BXSB 狼疮的候选基因

• 批准号: 8274814
• 负责人: CHANDRA MOHAN
• 金额: $ 25.4万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8274814
• 关键词: Age; Autoantibodies; Autoimmune Diseases; B-Lymphocytes; CXCL12 gene; CXCR4 gene; Candidate Disease Gene; Cell physiology; Chromosomes, Human, Pair 1; Development; Disease; Disease susceptibility; Dissection; Exhibits; Genes; Genetic; Genetic Polymorphism; Goals; In Vitro; Ligands; Lupus; Modeling; Molecular Genetics; Monocytosis; Mus; Myelogenous; Myeloid Cells; Nuclear; Pathogenesis; Pattern; Phenotype; Play; Positioning Attribute; Predisposition; Role; Stromal Cell-Derived Factor 1; Systemic Lupus Erythematosus; Testing; Y Chromosome; base; in vivo; interest; mouse model; therapeutic target

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.

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，以及涉及 B 细胞的几种细胞异常。骨髓细胞和其他 血统。狼疮的遗传基础仍有待解决。虽然几个的大概位置 小鼠狼疮的疾病易感位点已在许多不同的模型中得到阐明， 已识别基因座内的罪魁祸首基因仍然难以捉摸。尤其是 BXSB 菌株， 自发发展为狼疮。我们最近发现了 2 个看起来很有吸引力的潜在候选基因 作为该模型中狼疮的罪魁祸首，基于表达差异，有趣的序列 多态性并表现出功能差异。该提案的目的是测试候选人资格 这 2 个分子是 BXSB 狼疮的潜在罪魁祸首基因，并确定这些基因如何可能 使用体外和体内方法影响 B 细胞和骨髓细胞的功能。此外，我们将 评估狼疮中 SDF1/CXCR4 活性增强的起源和致病贡献。鉴于 目前，人们对狼疮的遗传学以及 B 细胞和骨髓细胞为何如此了解知之甚少。 狼疮过度活跃，拟议的研究可以极大地增进我们对这种疾病的了解。获得一个 在进行更有针对性的治疗之前，必须清楚了解狼疮的遗传和分子基础 可以针对这种疾病制定策略。