Identification of susceptibility gene(s) controlling autoantibody production in collagen induced arthritis

小鼠原性关节炎（CIA）是应用最广泛的自身免疫实验模型之一，具有许多与类风湿关节炎（RA）相似的特征。像类风湿性关节炎一样，CIA的易感性是由许多相互作用的基因控制的。我们和其他人估计，超过40个数量性状位点（QTL）控制着CIA发病机制的不同方面。在最近的一项研究中，我们对In (FVB/N和DBA/1J) F2后代进行了基因组扫描，以鉴定新的cia -QTL，并鉴定了位于第5染色体上的控制IgG2a抗胶原II抗体和疾病易感性的新QTL Cia27。随后，我们使用先进的杂交系将该位点细化到4.1 Mb区域，仅包含39个基因。本研究旨在鉴定Cia27的易感基因。为了实现这一目标，一系列经典和新颖的基因定位策略和功能分析将被执行。此外，还将进一步研究这种新型易感基因控制的疾病途径。

agen-induced arthritis (CIA) in the mouse is one of the most widely used autoimmune experimental models with many features similar to rheumatoid arthritis (RA). Like RA, the susceptibility to CIA is controlled by many interacting genes. We and others estimate that more than 40 Quantitiave Trait Loci (QTL), control different aspects of CIA pathogenesis. In a recent study we conduced a genome scan in in (FVB/N and DBA/1J) F2 progeny to identify novel CIA-QTLs and identified Cia27, a novel QTL on chromosome 5, controlling IgG2a anti collagen II antibody and disease susceptibility. We subsequently refined this locus using an advanced intercross line down to a 4.1 Mb region, containing only 39 genes. In this proposal we aim to identify the susceptibility gene for Cia27. To achieve this goal, a series classical and novel gene-mapping strategies and functional assays will be performed. Furthermore, the disease pathway controlled by this novel susceptibility gene will be investigated.