Imgt1^KK/Ta
QTL Variant Detail

Summary

• QTL variant: Imgt1^KK/Ta
• Name: impaired glucose tolerance 1; KK/Ta
• MGI ID: MGI:3038492
• QTL: Imgt1 Location: unknown Genetic Position: Chr6, cM position of peak correlated region/allele: 6.68 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: KK/Ta

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers decreased glucose tolerance compared to BALB/c. (J:88209)

Notes

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

J:88209

Linkage analysis using 93 microsatellite markers at an average spacing of 14 cM was performed on 208 KK/Ta x (BALB/c x KK/Ta)F1 backcross animals to identify QTLs associated with type 2 diabetes susceptibility. Parental strain KK/Ta exhibits type 2 diabetes phenotypes such as obesity, impaired glucose tolerance, hyperinsulinemia, hyperlipidemia, and fasting hyperglycemia compared to parental strain BALB/c. F1 hybrids show an intermediate phenotype.

Fbgl1 (fasting blood glucose level 1) mapped to mouse Chromosome 12 between 34 cM (D12Mit4) and 38 cM (D12Mit227) (LOD=4.5). This locus explains 11.8% of the phenotypic variance. Candidate genes mapping to this region are Abcb1b (Pgy1) and Tshr.

Fbgl2 mapped to10.1 cM on mouse Chromosome 15 near D15Mit225 (LOD=3.3). This locus explains 6% of the phenotypic variance. A candidate gene mapping to this region is Ghr. KK/Ta-derived alleles confer increased fasting blood glucose levels at Fbgl1 and Fbgl2.

Imgt1 (impaired glucose tolerance 1) mapped to 2.8 cM on mouse Chromosome 6 near D6Mit1 (LOD=4.0). This locus explains 11% of the phenotypic variance. Imgt1 colocalizes with Fglu, a previously mapped QTL for fasting blood glucose.

Tgl1 (triglyceride level 1) mapped to mouse Chromosome 8 between 47 cM (D8Mit242)and 56 cM (D8Mit166) (LOD=4.8). This locus explains 13% of the phenotypic variance. Homozygosity for KK/Ta-derived alleles confer increased serum triglyceride levels at Tgl1 (recessive inheritance). Tgl1 also shows suggestive linkage to hyperinsulinemia (LOD=2.2). A candidate gene mapping to this region is Lcat.

Tgls1 (triglyceride level suppressor 1) mapped to 59 cM on mouse Chromosome 4 near D4Mit336 (LOD=3.2). KK/Ta-derived alleles suppress serum triglyceride levels in a recessive manner at Tgls1. Tgls1 also shows suggestive linkage to body weight (LOD=2.1).

Tchol1 (total cholesterol level 1) mapped to 49.2 cM on mouse Chromosome 3 near D3Mit12 (LOD=4.0). This locus explains 11% of the phenotypic variance. KK/Ta-derived alleles confer increased serum total cholesterol in a dominantly-inherited manner at Tchol1 . Tchol1 colocalizes with Cq3 and authors suggest they may have the same underlying gene. A candidate gene mapping near Tchol1 is Txnip (Hyplip1). The Tchol1 locus is syntenic to human Chromosome 1q21-23.

References

• Original: J:88209 Shike T, et al., Susceptibility and negative epistatic loci contributing to type 2 diabetes and related phenotypes in a KK/Ta mouse model. Diabetes. 2001 Aug;50(8):1943-8
• All: 1 reference(s)