International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


Desrosiers M P
University of Ottawa

Co-Authors: Vidal S
Institutions: University of Ottawa

In mice, genes of the major histocompatibility complex (H2) and the natural killer gene complex (NKC) determine resistance to cytomegalovirus infection by alternate mechanisms. While H2 molecules are thought to act as receptors which modulate infection of individual cells, the activating NK cell receptor Ly49H triggers NK cell cytotoxicity against infected cells following engagement of the viral protein, m157. We have studied the genetic basis of resistance to infection with CMV in a Mus musculus inbred strain that is highly resistant to MCMV despite the absence of Ly49h. We analyzed the inheritance of the resistance phenotype in F2 population. Segregation analysis of MCMV resistance follows the bimodal distribution, which indicates the presence of several major effector loci in this population. Based on sequence analysis, a candidate gene for an alternate elicitor of resistance/susceptibility to MCMV in this strain has been identified as an activating NK cell receptor sharing high amino acid sequence homology to Ly49H. The role of this gene in viral resistance will be assessed by in vitro assays. These results underscore the functional diversity of the Ly49 family in host defense.

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