Tanidd1^CAST/EiJ
QTL Variant Detail

Summary

• QTL variant: Tanidd1^CAST/EiJ
• Name: TallyHo associated non-insulin dependent diabetes mellitus 1; CAST/EiJ
• MGI ID: MGI:2429610
• QTL: Tanidd1 Location: Chr19:53752597-53752718 bp Genetic Position: Chr19, cM position of peak correlated region/allele: 48.46 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: CAST/EiJ

Variant description

• Allele Type: QTL
• Inheritance: Dominant

Notes

Candidate Genes

J:99477

Authors used novel data mining tool ExQuest to identify novel candidate genes for existing diabesity QTLs. Next, candidate gene expression in the liver, adipose, and pancreas of diabesity-prone Tally Ho mice and diabesity-resistant C57BL/6J mice was assessed by quantitative PCR analysis. Several potential candidate genes, some with no previous association to diabesity QTLs, were identified. Since QTL intervals may be large and could contain hundreds or thousands of potential candidate genes, this method allows researchers to focus on those with strong potential as well as identify novel candidate genes.

Potential candidate genes for Iba4 (20 cM) on mouse Chromosome 19 as identified by ExQuest are Aldh1a1 (12 cM), Aldh1a7, Vldlr (20 cM), and Plce1. Vldlr exhibits 15.6-fold increased expression in the liver of Tally Ho compared to C57BL/6 animals. For QTL Afw8 (26 cM), potential candidate genes Pi4k2a, Cpn1, and Elovl3 (47 cM) were identified. For QTLs Nobq2 (47 cM) and Bglq13 (51 cM), potential candidate genes Ins1 (49 cM), Gpam (52 cM), and Acsl5 were identified. For QTLs Tanidd1 (50 cM) and T2dm2 (53 cM), potential candidate genes Gfra1, Pnlip (29 cM), Pnliprp1 (29 cM), and Pnliprp2 were identified. Pnliprp2 exhibits 21.8-fold decreased expression in the pancreas of Tally Ho animals in response to a 4% fat diet.

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

J:70227

Linkage analysis was performed on (C57BL/6J x TH)F1 x TH male backcross animals and (CAST/Ei x TH)F1 x TH male backcross animals to identify QTLs associated with diabetes-related phenotypes. The TH (TallyHo) strain is a mouse model for human non-insulin dependent diabetes mellitus (NIDDM). TH males develop hyperglycemia by 10-14 weeks of age whereas C57BL/6J and CAST/Ei males are normoglycemic. TH animals also exhibit increased body weight and fat pad weights compared to non-diabetic C57BL/6J and CAST/Eistrains. A locus associated with NIDDM, Tanidd1 (TallyHo associated NIDDM 1), mapped to mouse Chromosome 19 from 16 cM - 60 cM in both backcross sets (LOD = 3.1 at D19Mit103). Tanidd2 mapped to mouse Chromosome 13 from 5 cM - 70 cM in the C57BL6/J backcross (LOD = 4 at D13Mit148) and Tanidd3 mapped to mouse Chromosome 16 from 0 cM - 34 cM in the CAST/Ei backcross (LOD = 2.8 at D16Mit129). TH-derived alleles confer recessively inherited hyperglycemia at Tanidd1, Tanidd2, and Tanidd3. A QTL associated withbody weight, Tabw (TallyHo associated body weight), mapped to mouse Chromosome 7 from 0 cM - 44 cM (LOD = 3.9 at D7Mit231), and a QTL associated with fat pad weight, Tafat (TallyHo associated fat pad), mapped to mouse Chromosome 4 from 68 cM - 90 cM (LOD= 3.1 at D4Mit312). Animals homozygous for TH-derived alleles at Tafat exhibit lower fat pad weights than heterozygous animals, and animals homozygous for TH-derived alleles at Tabw exhibit lower body weights than heterozygous animals. The insulin gene, Ins1, maps near Tanidd1 and was considered as a candidate gene but sequence analysis failed to reveal differences between TH and C57BL/6J in the Ins1 promoter and coding regions.

References

• Original: J:70227 Kim JH, et al., Genetic analysis of a new mouse model for non-insulin-dependent diabetes. Genomics. 2001 Jun 15;74(3):273-86
• All: 1 reference(s)