Stxbp5l^T2dm1
QTL Variant Detail

Summary

• QTL variant: Stxbp5l^T2dm1
• Name: syntaxin binding protein 5-like; type 2 diabetes mellitus 1
• MGI ID: MGI:2429600
• Synonyms: Stxbp5l^T2dm1-BTBR
• QTL: Stxbp5l Location: Chr16:36935304-37205324 bp, - strand Genetic Position: Chr16, 26.32 cM

Variant origin

• Strain of Specimen: BTBR

Variant description

• Allele Type: QTL
• Mutation: Nucleotide substitutions
• Mutation details: The BTBR QTL allele contains a non-synonymous coding single nucleotide polymorphism (SNP; S912L) within the coding sequence and eight other SNPs in intergenic regions 5' and 3' to the gene that result in increased expression due to reduced proteosome degradation compared with the C57BL/6J QTL allele. (J:178002)
• Inheritance: Dominant

Notes

Significant interaction was detected between T2dm1 and T2dm2. Animals homozygous for BTBR-derived alleles at T2dm1 and homozygous for C57BL/6J-derived alleles at T2dm2 exhibit the highest fasting glucose levels.

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

J:65486

A Genome wide scan was performed on 160 (BTBR x C57BL/6J) F2-ob/ob intercross animals, using 99 informative markers at an average spacing of 16 cM, to identify loci affecting diabetes in obese animals. Neither parental strain BTBR nor C57BL/6J exhibit diabetes or obesity phenotypes, but lean male (BTBR x C57BL/6J) F1 hybrid animals develop severe hyperglycemia indicating the existence of diabetes susceptibility alleles in BTBR and C57BL/6J genetic backgrounds. Initial mapping indicate that mouse Chromosomes 2, 16 and 19 were involved in diabetic phenotypes. LOD values derived from multitrait composite interval mapping were used to further refine the map locations.

A locus associated with 8- and 10-week glucose and insulin levels, T2dm1 (type 2 diabetes mellitus 1), mapped to mouse Chromosome 16 with a LOD > 4.0 at D16Mit12. BTBR-derived alleles are dominant to C57BL/6J-derived alleles at T2dm1. T2dm2, a locus associated with 10-week insulin levels, mapped to mouse Chromosome 19 with a LOD >7.5 atD19Mit35. BTBR-derived alleles increase insulin levels by 38% in a dominant fashion at T2dm2. T2dm2 is also suggestively associated with glucose levels (LOD = 3.79, with C57BL/6J-derived alleles increasing glucose levels). T2dm3 mapped to mouse Chromosome 2 with a peak LOD score of >6.5 between D2Mit274 and D2Mit106 in association with insulin levels. T2dm3 appears to exhibit additive inheritance and maps near the agouti (a) and mahogany (Atrn, previously mg) genes. A suggestive locus for 8-week glucoselevels mapped to mouse Chromosome 4 (LOD = 3) and a suggestive locus for 8- and 10-week insulin levels mapped to distal mouse Chromosome 5 (LOD = 3.2 and 2.7, respectively).

References

• Original: J:65486 Stoehr JP, et al., Genetic obesity unmasks nonlinear interactions between murine type 2 diabetes susceptibility loci. Diabetes. 2000 Nov;49(11):1946-54
• All: 2 reference(s)