Dissection of the genetic complexity of arthritis using animal models

The exploding progress in genomic technology and knowledge now opens the possibility to actually identify the molecular mechanisms in disease. However, inflammatory diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS), are complex and polygenic and remain a challenge. One possible shortcut could be the use of inbred animals as models for RA and MS for the genetic analysis. These models have been extensively characterized and show a similar degree of complexity as the corresponding human diseases. Using these models linkage analysis followed by isolation of the loci in congenic strains have been shown to be highly efficient and have provided fundamental new knowledge on the genetic control of these diseases. The genetically controlled congenic strains are also useful as scientific tools. They can be used for the identification of the disease-associated genes and, thereby, the essential disease pathways that have been selected by nature. We know that this is possible since we have succeeded in identifying the genes within two of the congenic regions; the MHC class II gene Aq controlling immune response and the Ncf1 gene controlling oxidative burst. Both of these genes are associated with T cell activation and arthritis severity.