Dbsq1^C3H/HeJ
QTL Variant Detail

Summary

• QTL variant: Dbsq1^C3H/HeJ
• Name: diabetes susceptibility QTL 1; C3H/HeJ
• MGI ID: MGI:3693588
• QTL: Dbsq1 Location: unknown Genetic Position: Chr3, Syntenic

Variant origin

• Strain of Specimen: C3H/HeJ

Variant description

• Allele Type: QTL
• Inheritance: Recessive

Notes

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

J:116038

Linkage analysis was performed on 785 animals from a (BKS.Cg-m+/+Lepr^db x C3H/HeJ)F2 intercross to identify QTLs associated with diabetes susceptibility. Genome scan was performed using 203 microsatellite markers. Animals were analyzed in groups arranged by sex and homozygosity or heterozyosity at Lepr^db. Diabetes is more severe when Lepr^db is on a BKS genetic background compared to a C3H/HeJ genetic background. Body weight, fat pad weight, blood glucose concentration, and blood glucose during the intraperitoneal glucose tolerance test were measured in F2 animals. Loci reaching statistical significance of alpha^{0.01 are reported below.}

Fat pad weight mapped to 70.2 cM on mouse Chromosome 3 near D3Mit86 (LOD=5.78) in male F2 animals homozygous for Lepr. This locus explains 17% of the variance and is named Dbsq1 (diabetes susceptibility QTL 1). BKS-derived alleles at Dbsq1 confer increased fat pad weight with dominant inheritance.

Linkage to body weight at 7, 8, 9, 10 weeks of age and at sacrifice mapped to 35.8 cM on mouse Chromosome 15 near D15Mit107 (maximum LOD=6.64) in male F2 mice heterozygous for Lepr^db. This locus explains approximately 15% of the variance and is named Dbsq2 (diabetes susceptibility QTL 2). C3H/HeJ-derived alleles confer increased body weight with dominant inheritance.

Linkage to blood glucose concentration at 30, 60, and 120 minutes during the intraperitoneal glucose tolerance test mapped to 8 cM on mouse Chromosome 16 near D16Mit81 (maximum LOD=8.15)in male F2 animals heterozygous for Lepr^db. This locus explains approximately 16% of the variance and is named Dbsq3 (diabetes susceptibility QTL 3). C3H/HeJ-derived alleles at Dbsq3 confer increased blood glucose concentrations with dominant inheritance. Haplotype analysis was used to refine the Dbsq3 interval to a 4.6 Mb region between 8 Mb and 12.6 Mb. Two potential candidate genes in this region exhibiting amino acid polymorphisms between BKS and C3H/HeJ are Txndc11 and Mkl2.

Linkage to blood glucose concentration at 8 weeks of age and at sacrifice mapped to 2 independent locations on mouse Chromosome 2 in male F2 animals homozygous for Lepr^db. Dbsq4 (diabetes susceptibility QTL 4) is at 37.2 cM near D2Ucl3pa (maximum LOD=4.53). This locus explains approximately 15% of the variance. Dbsq5 is at 91.3 cM near D2Mit207 (maximum LOD=4.23). This locus explains 13% of the variance.

Dbsq6 (diabetes susceptibility QTL 6) mapped to 14.9 cM on mouse Chromosome 4 near D4Mit139 (LOD=5.3) in female F2 animals homozygous for Lepr^db. This locus is linked to plasma leptin levels and explains 17% of the variance.

Linkage to blood glucose concentration at 0 minutes during the intraperitoneal glucose tolerance test mapped to 10.9 cM on mouse Chromosome 9 near D9Mit1001 (formerly D8Mit112) (LOD=5.35) in male F2 animals heterozygous for Lepr^db. This locus explains 12% of the variance and is named Dbsq7 (diabetes susceptibility QTL 7). Linkage to fasting blood glucose concentration mapped to 35.8 cM near D9Mit208 - D9Mit182 (LOD=4.9) in male F2 animals heterozygous for Lepr^db. This locus explains 10% of the variance and is named Dbsq8 (diabetes susceptibility locus 8).

References

• Original: J:116038 Moritani M, et al., Identification of diabetes susceptibility loci in db mice by combined quantitative trait loci analysis and haplotype mapping. Genomics. 2006 Dec;88(6):719-30
• All: 1 reference(s)