Lith2^AKR/J
QTL Variant Detail

Summary

• QTL variant: Lith2^AKR/J
• Name: lithogenic gene 2; AKR/J
• MGI ID: MGI:2446825
• QTL: Lith2 Location: Chr19:49992158-49992298 bp Genetic Position: Chr19, cM position of peak correlated region/allele: 44.88 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: AKR/J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers resistance to gallstone formation compared to C57L/J.
• Inheritance: Recessive

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:66646

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-Lith1^S and AK.L-Lith1^S, 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.

References

• Original: J:66646 Paigen B, et al., Quantitative trait loci mapping for cholesterol gallstones in AKR/J and C57L/J strains of mice. Physiol Genomics. 2000 Nov 9;4(1):59-65
• All: 1 reference(s)