Identifizierung von Anfälligkeitsgenen, die die Produktion von Autoantikörpern bei kollageninduzierter Arthritis steuern

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.