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

在小鼠中，抗原诱导的关节炎（CIA）是最广泛使用的自身免疫性实验模型之一，其许多特征类似于类风湿性关节炎（RA）。像RA一样，CIA的易感性受许多相互作用的基因控制。我们和其他人估计超过40个数量性状基因座（QTL）控制CIA发病机制的不同方面。在最近的一项研究中，我们在FVB/N和DBA/1 J的F2后代中进行了基因组扫描，以鉴定新的CIA-QTL，并鉴定了Cia 27，一个位于第5染色体上的新QTL，控制IgG 2a抗II型胶原抗体和疾病易感性。随后，我们使用先进的互交系将该位点细化到4.1 Mb区域，仅包含39个基因。 在这项提案中，我们的目标是确定Cia 27的易感基因。为了实现这一目标，将进行一系列经典和新颖的基因定位策略和功能测定。此外，这种新的易感基因控制的疾病途径将进行调查。

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.