International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


A-K B Lindqvist
Lund University

Johannesson M, Johansson C M, Holmdahl R,
1) Lund University

To dissect the interaction between susceptibility loci for Collagen-Induced Arthritis (CIA) we have established a partial advanced intercross between congenic strains. This experimental set up is accompanied by statistical analysis of gene interaction.Rheumatoid arthritis (RA) is an autoimmune syndrome diagnosed by the American College of Rheumatology (ACR) criteria reflecting signs and symptoms of chronic erosive inflammation of diarthrodial joints. RA is characterized by symmetrical swelling and pain of the joints, stiffness and fatigue. The genetic influence is of polygenic nature where the different genes most likely interact in disease susceptibility. CIA in mice is a well established model for human RA and the model used in the present study.We have previously identified two main susceptibility loci for CIA in a (NOD.Q X C57Bl/10.Q) intercross, Cia9 on chromosome 1 and Cia2 on chromosome 2. Since both parental strains carry the H2q haplotype, the influence of the H2 complex could be disregarded. The Cia9 and Cia2 loci were confirmed in a backcross experiment using the same parental strains. Analysis of two-locus interaction of both crosses using the QTL analysis application R/qtl established a model of interaction between the Cia9 and Cia2 loci. To experimentally confirm this interaction model we have established a partial advanced intercross by intercrossing congenic strains for Cia9 and Cia2. By this experimental set up we can follow the arthritis development in all genotype-combinations of the two loci in a controlled manner and thereby gain insight into the mechanism of Cia9 and Cia2 in disease pathology.

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