Mobq2^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Mobq2^C57BL/6J
• Name: multigenic obesity QTL 2; C57BL/6J
• MGI ID: MGI:2156656
• QTL: Mobq2 Location: Chr6:15144273-15144495 bp 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: C57BL/6J

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Expression

In Structures Affected by this Mutation:

2 anatomical structure(s)

Notes

Candidate Genes

J:91835

The correlation between gene expression and dietary interaction was examined in a population of (BALB/cStCrlfC3H/Nctr x VY/WffC3Hf/Nctr-A(vy)/a)F1 animals. A/a and A/A^vy animals were placed on a 70% (calorie restricted) or 100% (non-restricted) diet andliver mRNA levels were assessed for over 18,000 genes using DNA microarrays. Twenty-eight known genes showing statistically significant differential expression between the 70% and 100% calorie diets and A/a and A/A^vy genotypes mapped near known diabesity QTLs. These genes may be considered further for candidate genes.

On mouse Chromosome 6, Smo (7.2 cM) and Flnc (8.5 cM) both show differential expression between restricted and unrestricted diets on the A/a background as well as differential expressionbetween A/a and A/A^vy animals on the restricted diet. D6Wsu176e (2 cM) shows differential expression between restricted and unrestricted diets on the A/A^vy background. Diabesity QTLs Fglu (16 cM), Mob2 (3.05 cM), and Bwtq3 (4 cM) maps near these candidate genes. Candidate genes for diabesity QTLs Nidd3n (35.5 cM), Obq13 (26.8 cM), Obq14 (43.5 cM), and Bw18 (35 cM) are Mad2l1 (30.3 cM) and Rab11fip5 (35.5 cM, formerly ERATO DOI 32e). Mad2l1 shows differential expression between A/a and A/A^vy animalsonboth the restricted and unrestricted diets. Rab11fip5 shows differential expression between A/a and A/A^vy animals on the restricted diet.

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

J:14189

Using MAPMAKER/QTL, mice from a backcross involving (C57BL/6J x Mus spretus)F1 x C57BL/6J were analyzed to identify quantitative trait loci that effect obesity. A locus for multigenetic obesity (Mob2) mapped on proximal mouse Chromosome 6 and exhibited a peak LOD score of 2.8 with D6Mit1.

J:24238

Mob1 and Mob2, two previously identified QTLs affecting obesity on mouse Chromosome 7 and mouse Chromosome 6, respectively, were confirmed in a (C57BL/6J x SPRET/Ei)F1 x C57BL/6J backcross population. Interestingly, parental strains C57BL/6J and SPRET/Eiare both lean.

In the present study Mob1 gave a LOD score of 4.6 at D7Mit8 in association with percent body water, and is significantly linked to hepatic lipase activity (LOD = 5.1). Mob1 also showed linkage to total plasma cholesterol (LOD = 4.4), bodymassindex (LOD = 2.9), body weight (LOD = 2.9), and HDL cholesterol level (LOD = 3.1). Animals heterozygous at Mob1 exhibit 25% increase in body fat compared to animals homozygous for C57BL/6J-derived alleles at Mob1. Congenic strains B10.129(5M)/nSN andB10.C(41N)/Sn carry 129/J-derived and BALB/cJ-derived alleles at Mob1, respectively, on a C57BL/10SnJ background. Animals from both congenic lines exhibit decreased fat pad weight, body weight, and plasma cholesterol compared to C57BL/10SnJ. B10.129(5M)/nSN also exhibits decrease in hepatic lipase activity. Possible candidate genes in the region of Mob1 are Snrpn, Tub, Ath3, Igf1r, Ins2 and Sult1a1.

Mob2 gave a peak LOD score of 4.8 at D6Mit1 in association with femoral fat pad weight. Mob2 also showed linkage to total plasma cholesterol (LOD = 3.4) and percent body water (LOD = 3.2). Animals heterozygous at Mob2 exhibit a 2-fold increase in femoral fat pad weight compared to animals homozygous for C57BL/6J-derived alleles at Mob2. A possible candidate gene for Mob2 is Lep (ob).

Two novel QTLs, Mob3 and Mob4, mapped to mouse Chromosome 12 and mouse Chromosome 15, respectively. Mob3 is associated with percent body fat with a LOD score of 4.8 at D12Mit27 on mouse Chromosome 12. HeterozygosityatMob3 results in 44% increase in body fat compared to animals homozygous for C57BL/6J-derived alleles at Mob3. A possible candidate gene for Mob3 is Tshr. Mob4 is associated with mesenteric fat pad weight with a LOD score of 3.4 at D15Mit13 on mouse Chromosome 15. Animals heterozygous at Mob4 exhibit 32% decrease in mesenteric fat pad weight compared to animals homozygous for C57BL/6J-derived alleles at Mob4. A possible candidate gene for Mob4 is Ghr. Mob1, Mob2, Mob3, and Mob4 do not appear to interact.

References

• Original: J:14189 Warden CH, et al., Coincidence of genetic loci for plasma cholesterol levels and obesity in a multifactorial mouse model. J Clin Invest. 1993 Aug;92(2):773-9
• All: 2 reference(s)