Ultrafine mapping of SNPs from mouse strains C57BL/6J, DBA/2J, and C57BLKS/J for loci contributing to diabetes and atherosclerosis susceptibility

Diabetes. 2005 Apr;54(4):1191-9. doi: 10.2337/diabetes.54.4.1191.

Abstract

The inbred mouse strain C57BLKS/J (BKS) carrying a mutation of the leptin receptor lepr(-/-) (BKS-db) is a classic mouse model of type 2 diabetes. While BKS was originally presumed to be a substrain of C57BL/6J (B6), it has become apparent that its genome contains introgressed regions from a DBA/2 (DBA)-like strain and perhaps other unidentified sources. It has been hypothesized that the strikingly enhanced diabetes susceptibility of BKS-db compared with B6-db is conferred by this introgressed DNA. Using high-density single nucleotide polymorphisms, we have mapped the DBA and other contaminating DNA regions present in BKS. Thus, approximately 70% of its genome appears to derive from B6, with approximately 20% from DBA and another 9% from an unidentified donor. Comparison with 56 diverse inbred strains suggests that this donor may be a less common inbred strain or an outbred or wild strain. Using expression data from a B6 x DBA cross, we identified differentially regulated genes between these two strains. Those cis-regulated genes located on DBA-like blocks in BKS constitute primary candidates for genes contributing to diabetes susceptibility in the BKS-db strain. To further prioritize these candidates, we identified those cis-acting expression quantitative trait loci whose expression significantly correlates with diabetes-related phenotypes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arteriosclerosis / genetics*
  • Chromosome Mapping
  • Diabetes Mellitus / genetics*
  • Genetic Predisposition to Disease
  • Genotype
  • Mice
  • Mice, Inbred C57BL / genetics*
  • Mice, Inbred DBA / genetics*
  • Polymorphism, Single Nucleotide
  • Receptors, Cell Surface / genetics
  • Receptors, Leptin

Substances

  • Receptors, Cell Surface
  • Receptors, Leptin