Background: Rheumatoid arthritis (RA) and Multiple Sclerosis (MS) are chronic inflammatory diseases, which are caused by genetic and environmental factors. Susceptible genes have been hard to find in man because of complex genetics of the diseases and the human population. Fortunately, good animal models are available. Pristine induced arthritis and experimental allergic encephalomyelitis in rats are such models. These models have been used to investigate the linkage of genome regions to disease phenotype in crosses between the susceptible DA rat and the resistant E3 rat. In these experiments a number of regions controlling disease onset, severity rend tonicity have been identified. Interestingly, several of these regions affect disease both in RA and MS. All major. Regions have been isolated as congener fragments in rats that will now be used to position ally clone the responsible genes. This project will focus on congener rats specifically controlling chronic inflammation. Cloning will be achieved by recombination selection complemented by new technologies in functional genomic and polemics. Objectives: To position ally clone gene(s) controlling tonicity in rat models of RA and MS and to elucidate the biological pathways affected by these genes. This knowledge will be used for development of new therapies for chronic inflammatory diseases. Methods: The project will be performed on genetically unique rats at the section for Medical Inflammation Research in Sweden. The genes will be cloned by recombination selection strategies witch are complemented by new techniques like micro array, real time PCR and 2D electrophoresis followed by mass-spectrometry, which are highly valuable and suitable for studies on complex diseases in animal models.
Call for proposal
See other projects for this call