International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)

Oral Presentation

Monday 18 November

20:15 - 20:30 HRS


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The Walter and Eliza Hall Institute

Co-Authors: Vikki Marshall, Rachel Burt, James Wagglen, Enmoore Lin
Institutions: The Walter and Eliza Hall Institute

There are well documented associations between host genetics and response to infection in humans. These are most evident in the case of malaria where many genetic diseases involving the red blood cell are found in geographic coincidence with malarial endemnicity. While association with diseases is relatively straightforward, analysis of other genetic resistance factors which are not so obvious in homozygotes are difficult in human populations. We have elected to use mouse models to study the genetically determined response in mice in an attempt to identify pathways that may be involved in the regulation of the pathophysiological consequence of disease in humans.We have mapped three loci in murine intercrosses which control various aspects of malarial infection. Two loci, Char1 and 2 control both outcome to infection and peak parasitaemia levels and Char3 controls clearance of parasites from the circulation. We have generated congenic mice for each locus and identified minimal congenic intervals still retaining a phenotype distinguishable from the backcross parental line. A BAC map has been generated for Cha1. This covers some 3Mb DNA on murine chromosome 9. Approximately 50% of this region has been used to generate BAC congenic animals. One line has a malarial phenotype different from the non-transgenic littermates. This line contains two overlapping BACs which have been sequenced and which contain 11 genes. Efforts to subdivide the region using further BAC transgenesis will be discussed.Congenic animals for these loci have been bred. These have novel phenotypes. Some of these have differences in red cell physiology which is likely to be related to the change in response to malarial infection. Animals congenic for the Char2 locus probably carry at least two loci which interact epistatically, At least one of these loci is red cell specific.

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