Experiment
Male animals from a (AKR/J x C57L/J)F1 x AKR/J backcross were typed for microsatellite markers at an average spacing of 20 cM to identify loci linked to cholesterol gallstone weight. When fed a lithogenic diet, inbred strain AKR/J is gallstone resistant while inbred strain C57L/J is gallstone susceptible. C57L/J susceptibility alleles appear to be dominant as (AKR/J x C57L/J)F1 hybrids are susceptible to gallstones when fed a lithogenic diet.
A major locus, Lith1, mapped to mouse Chromosome 2 from 30 cM - 80 cM with a LOD = 4.5 near D2Mit56 and is associated with the C57L/J-derived allele. Fig4 displays QTL interval mapping between D2Mit88 and D2Mit109 with a peak at D2Mit14a.
A second locus, Lith2, mapped to mouse Chromosome 19 from 40 cM - 85 cM with LOD =1.8 near D19Mit58 and is associated with the C57L/J-derived allele. Fig4 displays QTL interval mapping between D19Mit19 and D19Mit71 with a peak at D19Mit58.
Both loci were confirmed by constructing congenic strains carrying C57L/J-derived Lith1 or Lith2 on an AKR/J background. These congenics were named AK.L-Lith1S and AK.L-Lith1S, respectively. Both congenics retained the susceptibility phenotype of donor strain C57L/J.
A candidate gene for Lith1 is Abcb11 and a candidate gene for Lith2 isAbcc2.
Suggestive loci were also mapped to mouse Chromosome 6 with a maximum LOD = 2.3 at D6Mit25, mouse Chromosome 7 with a maximum LOD = 3.0 at D7Mit85, mouse Chromosome 8 with a maximum LOD = 1.3 at D8Mit40, mouse Chromosome 10 with a maximum LOD = 2.2 at D10Mit2, and mouse Chromosome X with a maximum LOD = 1.6 at DXMit46.