Hypism^PERA/EiJ
QTL Variant Detail

Summary

• QTL variant: Hypism^PERA/EiJ
• Name: hyperinsulinemia; PERA/EiJ
• MGI ID: MGI:3528051
• QTL: Hypism Location: unknown Genetic Position: Chr13, cM position of peak correlated region/allele: 26.25 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: PERA/EiJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased plasma insulin levels compared to C57BL/6J. (J:94548)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Animals heterozygous for C57BL/6J and PERA/EiJ alleles at Hypism exhibit increased insulin levels.

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

J:94548

Linkage analysis was performed on 167 animals from a (PERA/EiJ x B6.129S7-Ldlr^tm1Her/J)F1 x B6.129S7-Ldlr^tm1Her/J backcross to identify QTLs involved in metabolic syndrome (obesity, hypertension, insulin resistance, abnormal plasma lipids.) Male and female backcross animals homozygous for the Ldlr knockout mutation were placed on a Western diet and typed for 153 polymorphic markers at an average spacing of 10 cM. Parental strain PERA/EiJ is more susceptible to hyperglycemia, hyperleptinemia, hypertriglyceridemia, increased body fat and increased insulin compared to parental strain B6.129S7-Ldlr^tm1Her/J. F1 hybrid animals also exhibit susceptibility to metabolic syndrome phenotypes.

Linkage to atherosclerotic lesion area mapped to 69 cM on mouse Chromosome 2 near D2Mit405 (LOD=3.9). This locus is named Athla1 (atherosclerotic lesion area 1). Animals homozygous for C57BL/6J-derived alleles at Athla1 exhibit increased atherosclerotic lesion area. This locus explains 11% of the variance.

A locus on mouse Chromosome 4 named Mbsyd (metabolic syndrome) showed linkage to several metabolic syndrome traits. Mbsyd showed peak linkage to triglycerides (LOD=4.8) and body weight (LOD=4.0) at D4Mit143 (43 cM.) Animals heterozygous at Mbsyd exhibit increased plasma triglycerides and increased body weight. This locus explains 13% of the triglyceride variance and 11% of the body weight variance. The 1 LOD support interval for Mbsyd spans 22 cM - 50 cM. This locus includes the leptin receptor, Lepr, at 46.7 cM. Analysis of Lepr mRNA did not reveal differential mRNA expression between parental strains PERA/EiJ and B6.129S7-Ldlr^tm1Her/J.

A locus on mouse Chromosome 7 showed linkage to plasma HDL cholesterol in male animals at 53 cM near D7Mit253 (LOD=3.1). This locus is named Hdlcl1 (HDL cholesterol level 1). Animals homozygous for C57BL/6J-derived alleles at Hdlcl1 exhibit increased HDL cholesterol. This locus explains 18% of the variance.

A locus on mouse Chromosome 8 showed linkage to body weight in male animals at 16 cM near D8Mit291 (LOD=3.4). This locus is named Bdywt (body weight). Animals homozygous for C57BL/6J-derived alleles at Bdywt exhibit increased body weight. This locus explains 19% of the variance.

On mouse Chromosome 13, linkage to HDL cholesterol levels mapped to 32 cM near D13Mit139 (LOD=4.6) and linkage to insulin levels in male animals mapped to 48 cM near D13Mit144 (LOD=4.3). The HDL locus is named Hdlcl2 (HDL cholesterol level 2) and the insulin locus is named Hypism (hyperinsulinemia.) Animals heterozygous at Hdlcl2 exhibit increased HDL cholesterol and animals heterozygous at Hypism exhibit hyperinsulinemia. Hdlcl2 explains 26% of the HDL variance and Hypism explains 11% of the insulin variance.

Suggestive linkage to insulin levels in female animals mapped to 92 cM on mouse Chromosome 1 near D1Mit270 (LOD=2.9). Animals heterozygous at D1Mit270 exhibit increased insulin levels. This locus explains 16% of the variance.

Suggestive linkage to body weight in male animals mapped to 6 cM on mouse Chromosome 13 near D13Mit134 (LOD=2.9). Animals heterozygous at D13Mit134 exhibit increased body weight. This locus explains 16% of the variance.

References

• Original: J:94548 Seidelmann SB, et al., Quantitative trait locus mapping of genetic modifiers of metabolic syndrome and atherosclerosis in low-density lipoprotein receptor-deficient mice: identification of a locus for metabolic syndrome and increased atherosclerosis on chromosome 4. Arterioscler Thromb Vasc Biol. 2005 Jan;25(1):204-10
• All: 1 reference(s)