Loci of intestinal distress in cystic fibrosis knockout mice.
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.
Haston
Christina K
CK
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. christina.haston@mcgill.ca
Tsui
Lap-Chee
LC
D000483:Alleles; D000818:Animals; D020296:Animals, Congenic; D003433:Crosses, Genetic; D003550:Cystic Fibrosis / Q000235:genetics* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics* / Q000502:physiology; D007410:Intestinal Diseases / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015996:Survival Rate; D014886:Weaning
D005819:Genetic Markers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator