International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


Bureau JF, Levy Acobas F, Levillayer F, Brahic M, Szatanik M

Institut Pasteur, Paris, France

Characterizing genes of susceptibility to complex disorders is one of the most promising challenges at the beginning of the XXI century. The demyelinating disease induced by the persistent infection of Theiler’s virus in the mouse spinal cord is studied as a model for Multiple Sclerosis. Susceptibility to the infection amongst mouse strains depends mainly to the ability of their immune system to eliminate the virus.

By crossing and analyzing congenic strains between the SJL/J and the B10.S strains, two loci of susceptibility, named Tmevp2 and Tmevp3, were located on chromosome 10 close to the Ifng gene. We decided to characterize the Tmevp3 locus.

A cluster of cytokines containing at least 3 genes: Tmevpg1, Ifng, and Il-Tif/IL22 is an interesting region located at the telomeric part of the Tmevp3 interval since major loci of susceptibility between the SJL/J and the B10.S are expressed in the immune system. We decided to test this hypothesis by haplotyping this cluster in 15 strains: 11 laboratory strains with known susceptibility to the persistence of Theiler’s virus and 4 wild-type derived strains. We searched for polymorphism located in Tmevpg1, Ifng, Il22, and Mdm1/Mdm2, the 2 first genes centromeric to the cluster. The haplotype of laboratory strains are divided in at least two groups. The first group contains the SJL/J and the NZB strains and the second group the 9 other ones. The good correlation between these haplotypes and susceptibility to Theiler’s persistence strongly suggests that the Tmevp3 locus is located in this cluster.

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