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International Immunology, Vol. 14, No. 1, 79-85, January 2002
© 2002 Japanese Society for Immunology

Identification of susceptibility genes for experimental autoimmune encephalomyelitis that overcome the effect of protective alleles at the eae2 locus

Johan Jirholt, Anna-Karin Lindqvist, Jenny Karlsson, Åsa Andersson and Rikard Holmdahl

Section of Medical Inflammation Research, CMB, Lund University, I11 BMC, 221 84 Lund, Sweden

Correspondence to: J. Jirholt, AstraZeneca R & D Mölndal, 431 83 Mölndal, Sweden

We have previously identified a locus on mouse chromosome 15 (eae2) that regulates susceptibility to experimental autoimmune encephalomyelitis in a cross between the susceptible strain B10.RIII and the resistant strain RIIIS/J. In an effort to verify the protective effect from having two RIIIS/J alleles at eae2, the resistant locus was bred into the susceptible strain in homozygous form. However, the expected effect was not as clear as in the original study. This might be due to an epistatic effect conferred by several unidentified genes in the genome of the resistant strain or due to the environment by genotype interactions, possibly overcoming the effect of protective alleles at eae2. To further the genetic understanding in this disease, a genome-wide linkage screening approach was employed on an F2 intercross that carried the protective allele at eae2in homozygous form while the rest of the genome segregated between the B10.RIII and RIIIS/J strains as in the original investigation. In the present study we find one region on chromosome 7, not previously identified in this strain combination, that affects the disease at significant logarithm of the odds score and six regions showing suggestive evidence for linkage to disease phenotypes.

Keywords: congenic strain, disease susceptibility, epistasis, genetic crosses, linkage analysis, mouse, multiple sclerosis, quantitative trait

Transmitting editor: E. Möller


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