Hyplip2^MRL/MpJ
QTL Variant Detail

Summary

• QTL variant: Hyplip2^MRL/MpJ
• Name: hyperlipidemia 2; MRL/MpJ
• MGI ID: MGI:3511256
• QTL: Hyplip2 Location: Chr15:12402203-102896555 bp Genetic Position: Chr15, Syntenic

Variant origin

• Strain of Specimen: MRL/MpJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers increased atherosclerosis and decreased HDL cholesterol on an atherogenic diet compared to BALB/cJ. (J:53728)
• Inheritance: Dominant

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

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

J:53728

Genome scan using 105 polymorphic markers at an average spacing of 20 cM was performed on 189 (MRL/MpJ-Tnfrsf6^lpr x BALB/cJ)F2 animals to map QTLs associated with plasma lipid traits. Parental strain MRL/MpJ-Tnfrsf6^lpr exhibits increased HDL, VLDL, and triglycerides on both CHOW and high fat diets compared to parental strain BALB/cJ. Also, BALB/cJ is relatively resistant to atherosclerosis on a high fat diet whereas MRL/MpJ- Tnfrsf6^lpr is moderately susceptible. Animals were placed on a high fat diet for 8 weeks.

A locus on mouse Chromosome 5 near D5Mit10 (54 cM) showed linkage to unesterified cholesterol (LOD=4.1), total cholesterol (LOD=3.8), and VLDL (LOD=2.8) on a high fat diet. This QTL is named Lprq1 (lipoprotein QTL 1). Homozygosity for MRL/MpJ-derived alleles confer decreased lipid levels with a recessive mode of inheritance. Potential candidate genes mapping near Lprq1 are Scarb1 (Srb1, 68 cM) and Mvk (64 cM).

Hyplip2 mapped to 32 cM mouse Chromosome 15 near D15Mit17. Hyplip2 shows linkage to total cholesterol (LOD=11.1), VLDL (LOD=6.7), and unesterified cholesterol (LOD=4.6) on a high fat diet. Homozygosity for the MRL/MpJ-derived allele confers increased total cholesterol and VLDL. A potential candidate gene mapping near Hyplip2 is Srebf2 (48.5 cM).

A locus at 26 cM on mouse Chromosome 19 near D19Mit12 showed linkage to HDL (LOD=8.4) and total cholesterol (LOD=3.8) on the high fat diet. This locus is named Lprq2. Homozygosity for MRL/MpJ-derived alleles confer decreased HDL cholesterol on a high fat diet. An attractive candidate gene for Lprq2 is Fas (23 cM). Tnfrsf6 shows tight linkage to both anti-dsDNA antibody levels and HDL concentration.

A suggestive QTL for unesterified cholesterol (LOD=3.1) and total cholesterol (LOD=2.1)on aCHOW diet mapped to mouse Chromosome 8 near D8Mit242 (42 cM). Homozygosity for MRL/MpJ-derived alleles confer increased total cholesterol, VLDL, and unesterified cholesterol levels on a CHOW diet. A possible candidate gene mapping near this suggestive locus is Lcat (53 cM).

References

• Original: J:53728 Gu L, et al., Quantitative trait locus analysis of plasma lipoprotein levels in an autoimmune mouse model : interactions between lipoprotein metabolism, autoimmune disease, and atherogenesis. Arterioscler Thromb Vasc Biol. 1999 Feb;19(2):442-53
• All: 3 reference(s)