Obq5^KK/HlLt
QTL Variant Detail

Summary

• QTL variant: Obq5^KK/HlLt
• Name: obesity QTL 5; KK/HlLt
• MGI ID: MGI:2157358
• QTL: Obq5 Location: Chr9:28503333-41799326 bp Genetic Position: Chr9, cM position of peak correlated region/allele: 23.53 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: KK/HlLt

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased adiposity in female animals compared to C57BL/6J. (J:57787)
• Inheritance: Dominant

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Candidate Genes

J:91835

The correlation between gene expression and dietary interaction was examined in a population of (BALB/cStCrlfC3H/Nctr x VY/WffC3Hf/Nctr-A(vy)/a)F1 animals. A/a and A/A^vy animals were placed on a 70% (calorie restricted) or 100% (non-restricted) diet andliver mRNA levels were assessed for over 18,000 genes using DNA microarrays. Twenty-eight known genes showing statistically significant differential expression between the 70% and 100% calorie diets and A/a and A/A^vy genotypes mapped near known diabesity QTLs. These genes may be considered further for candidate genes.

On mouse Chromosome 9, Ets1 (15 cM) showed differential expression between the restricted and unrestricted diets on the A/A^vy background and between A/a and A/A^vy animals on both therestricted and unrestricted diets. Diabesity QTLs mapping near Ets1 are Bwtq4 (8 cM) and Obq5 (19 cM). A candidate gene for diabesity QTL Dob2 (60 cM) is Cacna2d2 (60 cM). Cacna2d2 shows differential expression between the restricted and unrestricted diets on a A/a background.

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

J:57787

The authors investigated the inheritance of adiposity and related traits in the obese, diabetes-prone KK/H1Lt (KK) and the lean, normoglycemic C57BL/6J (B6) strains, their F1 hybrids, and a large intercross generation. Adiposity index (A1) was defined as the sum of four fat depot weights divided by body weight. A peak lod score of 7.0 for A1 was found on proximal Chromosome 9. Analysis of males and females revealed that gender had a profound effect on the magnitude of the Chromosome 9 A1 QTL (lod = 6.3 in females and lod = 2.7 in males P<0.001). This QTL was designated as Obq5 and peaked between D9Mit66 and D9Mit328 in females and accounted for 17% of the phenotypic variation in females. In males the Chromosome 9 lod score peaked 2 cM distal to D9Mit65.It is likely that the same QTL is acting in both genders. At D9Mit328, the marker close to the Obq5 peak, females homozygous for the B6 allele have a mean A1 ~30% lower than females bearing either one or two KK alleles. Obq5 also had effects on other traits in females: inguinal and gonadal fat pad weights as a percentage of body weight (lod = 3.1 and 2.7 respectively), retroperitoneal fat % (lod = 4.5), body weight (lod = 4.8), leptin (lod = 3.4) and mesenteric fat % (lod = 2.4). In males Obq5 has effects on mesenteric fat % (lod = 4.2), inguinal fat % (lod = 3.2), body weight (lod = 3.2) and leptin (lod = 2.4).

References

• Original: J:57787 Taylor BA, et al., Gender-influenced obesity QTLs identified in a cross involving the KK type II diabetes-prone mouse strain. Mamm Genome. 1999 Oct;10(10):963-8
• All: 1 reference(s)