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Loci of intestinal distress in cystic fibrosis knockout mice

Program of Genetics and Genomic Biology, Research Institute, The Hospital for Sick Children, and Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada

The strain-dependent survival of cystic fibrosis (CF) knockout mice has been used to map a modifier of CF, Cfm1, in mice and, subsequently, in humans. To identify additional modifiers of the CF phenotype, in this study, the survival of F2 CF mice derived from a cross between congenic C57BL/6J CF and BALB/cJ CF heterozygotes was followed up to 12 wk of age. A genome-wide linkage scan completed in F2 CF mice revealed a chromosome 10 locus (P = 1.2 x 10^-4) to predict for intestinal distress in CF male mice. An X chromosome locus for which non-Mendelian inheritance favoring B6 alleles in the surviving CF mice and BALB alleles in mice of a control population, was identified. The survival of female mice, both F2 CF and F2 control, was linked to loci on chromosomes 3 and 5. The identification of additional putative CF modifier loci may permit further genetic dissection of the complex CF phenotype.

modifier gene; transmission distortion

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