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Physiol. Genomics (November 19, 2002). doi:10.1152/physiolgenomics.00114.2002
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Articles in PresS, published online ahead of print November 19, 2002
Physiol Genomics, 10.1152/physiolgenomics.00114.2002
Submitted on September 3, 2002
Accepted on November 7, 2002

LOCI OF INTESTINAL DISTRESS IN CYSTIC FIBROSIS KNOCKOUT MICE

Christina K Haston1* and Lap-Chee Tsui1

1 Genetics and Genomic Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

* To whom correspondence should be addressed. E-mail: christina.haston{at}mcgill.ca.

The strain dependent survival of cystic fibrosis (CF) knockout mice has been used to map a modifier of cystic fibrosis, 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 weeks 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.




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