Dbm1^A/J
QTL Variant Detail

Summary

• QTL variant: Dbm1^A/J
• Name: diabetes modifier 1; A/J
• MGI ID: MGI:3664316
• QTL: Dbm1 Location: Chr6:78606487-121092347 bp Genetic Position: Chr6, cM position of peak correlated region/allele: 41.25 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: A/J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers increased plasma glucose concentration, increased plasma insulin concentration, and increased body weight in males compared to C57BL/6J. (J:112869)

Notes

The effect of Dbm1 is observed in males heterozygous for Ins2^Akita.

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

J:112869

Modifiers of type 2 diabetes were mapped using a large F2 intercross derived from parental strains C57BL/6-Ins2^Akita/Slc and A/JSlc. Genome scan was performed with 281 polymorphic markers. Animals were phenotyped at 10 weeks of age for plasma glucose concentration, immunoreactive insulin concentration, and intraperitoneal glucose tolerance test (IPGTT). C57BL/6-Ins2^Akita/Slc exhibits non-obese hypoinsulinemic diabetes whereas A/JSlc is non-diabetic.

Dbm1 (diabetes modifier 1) was identified at 38 cM on mouse Chromosome 6 near D6Mit31 in male F2 animals heterozygous for Ins2^Akita. The QTL interval is flanked by D6Mit3 (33.5 cM) and D6Mit216 (58.6 cM). This locus is associated with fasting plasma glucose (LOD=4.12) and plasma glucose at 120 minutesof IPGTT (LOD=3.91). Dbm1 also shows suggestive linkage to plasma glucose at 30 (LOD=2.02) and 60 minutes (LOD=2.48) during IPGTT. Dbm1 is also linked to plasma insulin at 120 of the IPGTT (LOD=4.52) and body weight (LOD=6.32) in male F2 animals homozygous for wild type Ins2 alleles. A/JSlc-derived alleles at Dbm1 confer increased plasma glucose at all time points, increased plasma insulin, and increased body weight. Previously identified diabetes QTL Nidd3n (35.5 cM) maps near Dbm1. Potential candidate genes include Cntn4, Il5ra (46 cM), Itpr1 (48 cM), and Pparg (52.7 cM). Suggestive linkage to fasting plasma glucose (LOD=3) and plasma glucose at 120 minutes (LOD=3.8) mapped to D6Mit84 (0.66 cM).

Dbm2 (diabetes modifier 2) was identified near D11Mit254(71 cM) and D11Mit203 (74.5 cM) on mouse Chromosome 11 in male F2 animals homozygous for wild type Ins2 alleles. The QTL interval is flanked by D11Mit213 (55 cM) and D11Mit48 (77 cM). This locus is linked to fasting plasma glucose (LOD=2.45), and plasma glucose at 30 (LOD=3.69), 60 (LOD=4.5), 90 (LOD=5.78), and 120 minutes (LOD=6.3) of the IPGTT. C57BL/6-derived alleles at Dbm2 confer increased plasma glucose concentrations and decreased glucose clearance. Dbm2 is syntenic to human Chromosome 17q24-q25. Potential candidate genes include Sstr2 (69 cM), Gpr142, Galk1 (78 cM), and Acox1. Nidd4 (68 cM) is a previously identified diabetes QTL located near Dbm2.

Dbm3 mapped to mouse Chromosome 14 between D14Mit98 (3 cM) and D14Mit82 (19.5 cM) in male F2 animals heterozygousfor Ins2^Akita. Peak linkage occurs at 5.5 cM (D14Mit207). This locus is linked to fasting plasma glucose (LOD=4.17), and plasma glucose at 30 (LOD=3.41), 60 (LOD=2.26), and 120 minutes (LOD=2.02) during the IPGTT. C57BL/6-derived allelesatDbm3 conferincreased plasma glucose concentrations. Nidd2n (22.5 cM) is a previously identified diabetes QTL located near the Dbm3 interval.

Dbm4 mapped to mouse Chromosome 15 in male F2 animals heterozygous for Ins2^Akita. This locus exhibits significant linkageto fasting plasma glucose concentration (LOD=6.17) near D15Mit233 (29.2 cM) and D15Mit63 (34.2 cM). Dbm4 also exhibits suggestive linkage to plasma glucose at 30 (LOD=3.24), 60 (LOD=2.37), and 120 minutes (LOD=2.91) during the IPGTT. C57BL/6-derived alleles at Dbm4 confer increased plasma glucose at all time points. Female F2 animals heterozygous for Ins2^Akita exhibit weak linkage to fasting plasma glucose at Dbm4 (LOD=2.08). Human Chromosome 8q24 is syntenic to the Dbm4 interval. Potential candidategenes in this region include Adcy8 (37.5 cM), Oc90 (37.5 cM), Tg (36.4 cM), and St3gal1 (formerly Siat4a).

References

• Original: J:112869 Takeshita S, et al., Diabetic modifier QTLs identified in F2 intercrosses between Akita and A/J mice. Mamm Genome. 2006 Sep;17(9):927-40
• All: 2 reference(s)