International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)


G11. Establishment of Congenic Strains Retaining QTLs that Confer Resistance/Susceptibility to Collagen-Induced Arthritis in Mice

D. A. Stephenson1,2, K. Chotti1, M.C. Hannibal3,4, E. Chi3, L. Hood4 and G.A. Carlson1
1 McLaughlin Research Institute, Great Falls MT 59405 USA,
2
Stowers Institute for Medical Research, Kansas City MO 64110 USA,
3
University of Washington, Seattle WA 98195 USA,
4
Institute for Systems Biology, Seattle WA 98105 USA

When immunized with type II chicken collagen, the mouse strain DBA/1J exhibits inflammation of the paws and joint damage. The H2 identical strain SWR/J is resistant to this form of induced arthritis. Initial genetic analysis of F2 offspring between these strains suggested that there were regions on chromosomes (chr) 2, 4, 10, 14 and 18 that contributed to this phenotype. Using a marker-assisted "speed congenic" breeding program, these regions were transferred from one strain background to the other. None of the SWR/J congenics containing the DBA/1J chromosomal regions responded to collagen immunization with clinical signs of paw inflammation. This supports evidence that multiple loci in the SWR/J strain confer arthritis resistance. Of the DBA/1J congenic strains, the presence of the SWR/J region from chr 2 conferred recessive resistance whereas the region from chr 14 enhanced the incidence and severity of the susceptible strain. As both chromosomal regions are relative large (~ 10cM on chr 2 and 20cM on chr 14), we are in the process of setting up crosses to further refine the interval by recombination. We are also in the process of constructing radiation chimeras to establish whether the susceptibility lies in the humoral or cellular immune compartments.


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