Ultrafine mapping of SNPs from mouse strains C57BL/6J, DBA/2J, and C57BLKS/J for
loci contributing to diabetes and atherosclerosis susceptibility.
Authors Davis RC, Schadt EE, Cervino AC, Péterfy M, Lusis AJ
Submitted By Richard Davis on 2/11/2009
Status Published
Journal Diabetes
Year 2005
Date Published 4/1/2005
Volume : Pages 54(4) : 1191 - 1199
PubMed Reference 15793261
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.

Investigators with authorship
Richard DavisUniversity of California Los Angeles