International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


Oral Presentation

Monday 18 November

21:30 - 21:45 HRS

A SUBPHENOTYPE BASED STRATEGY TO DISSECT A GENE CLUSTER ON MOUSE CHROMOSOME 3 ASSOCIATED WITH SEVERAL AUTOIMMUNE DISEASES

M Johannesson
Medical Inflammation research, Lund University

Co-Authors: Wester L, Selva NK, Holmdahl M, Holmdahl R
Institutions: Medical Inflammation Research, Lund University

A locus on chromosome 3 that controls severity of both CIA (collagen-induced arthritis) and EAE (experimental allergic encephalomyelitis) has earlier been identified (denoted eae3 and cia5). In a novel congenic strain, B10.RIIIEae3, we have now confirmed both linkages. For both diseases, RIIIS/J genes on B10.RIII background made the disease less severe.Many loci have been mapped in different F2-crosses but it has been difficult to identify the actual genes. Several of the loci analysed with congenic strains have turned out to be a cluster of genes controlling the complex disease. With this in mind we chose a new strategy to dissect eae3 and cia5. When investigating the congenic strain, we did not only look at the diseases mapped in the original crosses, we also investigated subphenotypes related to the diseases. For example, B10.RIIIEae3 cells showed a lower ability to present antigen and they were also resistant to antibody transfer-induced arthritis (TIA - a disease that the B10.RIII mice are highly susceptible to). These results suggest that different genes in the fragment are regulating different phases of CIA. To get an idea of which genes, we compared the gene expression in B10.RIIIEae3 and B10.RIII mice and found that several genes located in the region are down regulated; again indicating that more than one gene is involved. This locus has been mapped for several complex diseases (arthritis, encephalomyelitis and diabetes) in both mouse and rat and it will be important to have well defined phenotypes in order to identify the responsible genes.


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