Mice expressing an XRCC1 truncated protein are at increased risk for insulin resistance

Insulin resistance is a metabolic disorder that is highly prevalent in older populations. Mice expressing a truncated X-ray repair cross-complementing protein 1 (XRCC1tp) have normal repair of single-stranded breaks (SSBs) but are sensitive to alkylating agents. XRCC1tp mice thus provide a model to study perturbations in physiological function, such as metabolism, in the presence of normal DNA repair but attenuated XRCC1 activity. XRCC1tp male mice at six months of age fed a diet high in fat (lard) and sugar (sucrose) (HFSD) for three months showed a significant delay in glucose clearance, indicative of insulin resistance. These mice also had a decrease in respiratory exchange ratio, suggesting a change in the way fats and carbohydrates are used as a fuel source. Mechanisms for these observations are of interest, since there is a suggestion that XRCC1 is involved in glucoregulatory pathways, and XRCC1tp mice would provide an excellent model to pursue these studies in an age-related manner.