Lith24^DBA/2J
QTL Variant Detail

Summary

• QTL variant: Lith24^DBA/2J
• Name: lithogenic gene 24; DBA/2J
• MGI ID: MGI:2682406
• QTL: Lith24 Location: Chr2:80005954-80006113 bp Genetic Position: Chr2, Syntenic

Variant origin

• Strain of Specimen: DBA/2J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers susceptibility to gallstone formation compared to CAST/Ei. (J:85813)
• Inheritance: Dominant

Notes

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

J:85813

Linkage analysis was performed on a population of (CAST/Ei x DBA/2J)F2 animals to identify QTLs associated with cholesterol gallstones. Parental strain CAST/Ei is susceptible to gallstone formation whereas parental strain DBA/2 is resistant. Interestingly, (CAST/Ei x DBA/2J)F1 females are completely resistant to gallstone formation whereas F2 males exhibit 100% incidence of cholesterol gallstones. Animals were placed on a lithogenic diet for 8 weeks to promote the gallstone phenotype. CAST/Ei parentals also exhibit increased hepatic bile cholesterol concentration compared to parental strain DBA/2J.

A significant QTL on chromosome 2 was identified that colocalized with the previoulsy identified Lith1 QTL. [Curator note: Because Lith1 was originally mapped using a (AKR/J x C57L/J)F1 x AKR/J backcross (J:66646), we consider the current study a separate mapping experiment and have named the QTL Lith24.] Lith24 mapped to mouse Chromosome 2 at D2Mit94. Lith24 reached significant linkage to gallstone presenceat 52 cM with LOD=3.8 and reached suggestive linkage to aggregated cholesterol monohydrate crystals at 46 cM with LOD=2.8. The QTL range of Lith24 extends from 40 cM - 60 cM on mouse Chromosome 2. DBA/2J-derived alleles confer dominantly inherited susceptibility to cholesterol gallstone formation at Lith24.

A novel QTL named Lith6 was identified in association with aggregated cholesterol monohydrate crystals at 54 cM on mouse Chromosome 6 with LOD=3.8 at D6Mit62. The QTL range of Lith6 extends from 40 cM - 70 cM. CAST/Ei-derived alleles confer dominantly inherited susceptibility to cholesterol gallstone formation at Lith6. Slco1a1 and Pparg are candidate genes for Lith6 and both show differential expression between CAST/Ei and DBA/2J.

Another novel QTL on proximal mouse Chromosome 6 near D6Mit86, Lith10, is linked to gallstone number reaching peak significanceat 4 cM with LOD=3.6. Lith10 is also suggestively linked to gallstone presence at 0 cM with LOD=2.8. The QTL range of Lith10 extends from approximately 0 cM - 10 cM. DBA/2J-derived alleles confer recessively inherited susceptibility to gallstone formationat Lith10.

Lith11 mapped to 58 cM on mouse Chromosome 8 in association with gallstone number. Lith11 reached peak significance at D8Mit88 with LOD=3.3. The QTL range of Lith11 extends from 48 cM - 60 cM. DBA/2J-derived alleles confer recessively inherited susceptibility to gallstone formation at Lith11.

References

• Original: J:85813 Lyons MA, et al., Lith6: a new QTL for cholesterol gallstones from an intercross of CAST/Ei and DBA/2J inbred mouse strains. J Lipid Res. 2003 Sep;44(9):1763-71
• All: 1 reference(s)