| Summary: | Type 2 diabetes (T2D) is a major risk for atherosclerosis and its complications. <i>Apoe</i>-null (<i>Apoe</i><sup>−/−</sup>) mouse strains exhibit a wide range of variations in susceptibility to T2D and carotid atherosclerosis, with the latter being a major cause of ischemic stroke. To identify genetic connections between T2D and carotid atherosclerosis, 145 male F2 mice were generated from LP/J and BALB/cJ <i>Apoe</i><sup>−/−</sup> mice and fed 12 weeks of a Western diet. Atherosclerotic lesions in the carotid arteries, fasting, and non-fasting plasma glucose levels were measured, and genotyping was performed using miniMUGA arrays. Two significant QTL (quantitative trait loci) on chromosomes (Chr) 6 and 15 were identified for carotid lesions. The Chr15 QTL coincided precisely with QTL <i>Bglu20</i> for fasting and non-fasting glucose levels. Carotid lesion sizes showed a trend toward correlation with fasting and non-fasting glucose levels in F2 mice. The Chr15 QTL for carotid lesions was suppressed after excluding the influence from fasting or non-fasting glucose. Likely candidate genes for the causal association were <i>Tnfrsf11b</i>, <i>Deptor</i>, and <i>Gsdmc2</i>. These results demonstrate a causative role for hyperglycemia in the development of carotid atherosclerosis in hyperlipidemic mice.
|
|---|