Nidd4^TSOD
QTL Variant Detail

Summary

• QTL variant: Nidd4^TSOD
• Name: non-insulin-dependent diabetes mellitus 4; TSOD
• MGI ID: MGI:3036082
• QTL: Nidd4 Location: Chr11:113810136-113810253 bp Genetic Position: Chr11, cM position of peak correlated region/allele: 79.52 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: TSOD

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased blood glucose levels compared to BALB/cA. (J:55285)
• Inheritance: Recessive

Expression

In Structures Affected by this Mutation:

1 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 11, candidate genes for diabesity QTL Nidd4n (2 cM) are Dbn1 (34 cM- **Note: Location of Dbn1 is 34 cM on mouse Chromosome 13 according to mapping data in the MGI database**) and Dvl2 (36.5 cM). Both Dbn1 and Dvl2 show differential expression on the restricted and unrestricted diets on the A/A^vy background.

Candidate genes for diabesity QTLs Nidd1n (31 cM), Bwtq5 (27.8 cM), Wt10q3 (32 cM), Wt6q3 (36 cM) are Nola2 (28.5 cM, formerly Nhp2), Sept8 (28.75 cM), Skp1a (31 cM), and Mpdu1 (39 cM). Skp1a and Nola2 both show differential expression between restricted and unrestricted diets on the A/A^vy background. Sept8 shows differential expression between A/a and A/A^vy animals on the restricted diet.

Candidate genes for diabesity QTLs Wg4 (46 cM) and Bw4 (55 cM) are Dusp14 (48 cM), Spag7 (42 cM), Derl2 (42 cM, formerly Flana), Sfrs1 (49 cM), and Rara (57.8 cM). Dusp14, Derl2, and Spag7 all show differential expression between A/a and A/A^vy animals on the restricted diet. Sfrs1 shows differential expression between the restricted and unrestricted diets on the A/a background. Rara shows differential expression between the restricted and unrestricted diet on the A/a background as well as between A/a and A/A^vy animals on the restricted diet.

Fasn (72 cM) and Grb2 (75 cM) are candidate genes for diabesity QTL Nidd4 (68 cM). Fasn shows differential expression between restricted and unrestricted diets on the A/A^vy background while Grb2 shows differential expression between A/a and A/A^vy animals on the unrestricted diet.

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

J:55285

TSOD male mice exhibit both obesity and diabetes enabling that strain to be used in a cross with BALB/cAJcl to elucidate the genetic basis for the phenotype. (BALB/cAJcl x TSOD)F1s and (TSOD x BALB/cAJcl)F1s were intercrossed to provide F2 populations for genotyping using SSLP markers.

A major gene on mouse Chromosome 11 effecting glucose pheotypic levels (marker Nidd4) was significantly associated with D11Mit128(LOD 12.3).

References

• Original: J:55285 Hirayama I, et al., Genetic analysis of obese diabetes in the TSOD mouse. Diabetes. 1999 May;48(5):1183-91
• All: 1 reference(s)