Dbsty2^NZO/HlLt
QTL Variant Detail

Summary

• QTL variant: Dbsty2^NZO/HlLt
• Name: diabesity 2; NZO/HlLt
• MGI ID: MGI:2156063
• QTL: Dbsty2 Location: Chr5:93445064-93445225 bp Genetic Position: Chr5, cM position of peak correlated region/allele: 47.29 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: NZO/HlLt

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased adiposity compared to NON/Lt. (J:65256)
• Inheritance: Dominant

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Dbsty2 shows evidence of complex interactions with other diabesity loci.

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 5, Pdgfra (42 cM) showed differential expression between A/a and A/A^vy animals on the unrestricted diet. Diabesity QTLs Dbsty2 (45 cM), Bw8 (42 cM), and Bwob (44 cM) map near this candidate gene. Another candidate gene, Shrm (52 cM), showed differential expression between the restricted and unrestricted diets on the A/a background as well as between A/a and A/A^vy animals on the restricted diet. Diabesity QTL Igfbp3q1 (58 cM) maps near Shrm. Mdh2 (78 cM) shows differential expression between the restricted and unrestricted diets on a A/A^vy background. Diabesity QTL Bw13 (81 cM) maps near candidate gene Mhd2.

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

J:65256

Genome scan at an average density of 20 cM was performed on a population of 203 NON/Lt x (NZO/HlLt x NON/Lt)F1 backcross male animals to identify loci associated with diabesity. The New Zealand Obese (NZO) strain develops early onset diabetes, and exhibits impaired glucose tolerance (IGT), insulin resistance and leptin resistance. The Nonobese Nondiabetic (NON) strain does not develop diabetes or obesity, exhibits normal leptin levels, but shows IGT and low insulin responses. A broad QTL was detected on mouse Chromosome 1 from 8.3 cM - 43.1 cM and encompasses a variety of diabesity traits such as increased body weight, elevated plasma glucose levels, and early hyperinsulinemia. This locus, Dbsty1 (diabesity), appears to peak at approximately 21 cM near D1Mit123 with a LOD = 9.36 for body weight at 8 weeks of age. Dbsty2 is associated with adiposity index and maps to mouse Chromosome 5 at 45 cM with a LOD = 3.86 at D5Mit7. Dbsty3 maps to mouse Chromosome 12 from 45 cM - 53 cM with a peak LOD = 4.88 at D12Mit231 and is associated with body mass index, adiposity index, and leptin levels. Dbsty4 maps to mouse Chromosome 15 at approximately 49.6 cM with a peak LOD = 3.55 at D15Mit159 and is associated with plasma glucose. Inheritance of NZO-derived alleles atdiabesity QTLs act to increase diabesity traits. Suggestive QTLs mapped to mouse Chromosome 3 for plasma insulin levels (LOD = 2.53 at D3Mit22), mouse Chromosome 6 for body weight, body mass index, plasma insulin, adiposity index, and leptin levels (peakLOD = 3.42 at D6Mit123), mouse Chromosome 13 for body mass index (LOD = 2.03 at D13Mit53), and mouse Chromosome 18 for body mass index and adiposity index (LOD = 2.47 at D18Mit60). Complex interactions were detected among the diabesity QTLs as well as other loci. See article for details.

References

• Original: J:65256 Reifsnyder PC, et al., Maternal environment and genotype interact to establish diabesity in mice. Genome Res. 2000 Oct;10(10):1568-78
• All: 2 reference(s)