Tabw2^TALLYHO/Jng
QTL Variant Detail

Summary

• QTL variant: Tabw2^TALLYHO/Jng
• Name: tally ho associated body weight 2; TALLYHO/Jng
• MGI ID: MGI:3603216
• QTL: Tabw2 Location: Chr6:46912919-136400690 bp Genetic Position: Chr6, Syntenic

Variant origin

• Strain of Specimen: TALLYHO/Jng

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased body weight and increased plasma glucose compared to C57BL/6J.
• Inheritance: Recessive

Expression

In Structures Affected by this Mutation:

3 anatomical structure(s)

Notes

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

J:100831

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 are normoglycemic. TH males also exhibit increased body weight and fat pad weights compared to C57BL/6J males. Tabw2 (tally ho associated body weight 2) on mouse Chromosome 6 was identified by linkage analysis of a population of (C57BL/6J x TH)F1 x TH male backcross animals. Tabw2 mapped near D6Mit230 (43 cM) with TH-derived alleles conferring increased plasma glucose and body weight (recessive mode of inheritance). This locus accounts for 11% of the plasma glucose variance and 16% of the body weight variance. Tabw2 appears to interact with Tanidd1 on mouse Chromosome 19. Animals homozygous for TH-derived alleles at both Tabw2 and Tanidd1 exhibit significantly increased plasma glucose compared to animals heterozygous at both loci or animals heterozygous at Tabw2 and homozygous for TH-derived alleles at Tanidd1.

Tabw2 congenic animals with TH-derived DNA between D6Mit273 (19.1 cM) and D6Mit339 (65.5 cM) on a C57BL/6J genetic background were constructed. At 4 weeks of age on a CHOW diet, B6.TH-Tabw2 congenic animals exhibit increased body weight compared to C57BL/6J parentals. When placedon a high fat, high sucrose diet, B6.TH-Tabw2 congenics gain more weight and fat pad depots than C57BL/6J.

The Tabw2 locus was fine-mapped in 430 male (C57BL/6J x TH)F2 animals and resolved to a 15 cM interval extending distal of D6Mit102 (38.5 cM). TheLOD score peaks near D6Mit108 (48 cM, LOD=12.1). Previously identified obesity QTL mapping to this interval include Bwq2 (35 cM) and Obq14 (43.5 cM). Potential candidate genes mapping to this interval are Rab7 (38.5 cM), Trh (40 cM), Ghrl (49.7 cM), and Hrh1 (49 cM). However, sequence analysis of Hrh1 did not reveal coding region differences between TH and C57BL/6J, nor were expression differences observed via RT-PCR.

Tabw2 is syntenic to loci on human Chromosome 3p26-p24, 3p14, 3q13, and 3q21-q24. Body mass index (BMI) has been mapped to human Chromosome 3q22, and another locus for BMI and abdominal fat has been mapped to human Chromosome 3p26-p24.

References

• Original: J:100831 Kim JH, et al., Type 2 diabetes mouse model TallyHo carries an obesity gene on chromosome 6 that exaggerates dietary obesity. Physiol Genomics. 2005 Jul 14;22(2):171-81
• All: 5 reference(s)