Genetic analysis of a murine QTL for diet restriction on chromosome 15

Abstract

Diet restriction (DR), the implementation of a reduced calorie diet, without starvation, increases lifespan in a number of model organisms including mammals. How DR extends lifespan remains unclear. Genetic studies have shown that life extension is not a universal response to DR; instead, the effects of DR are strain dependent. We previously mapped a quantitative trait locus (QTL) specifying differential response to DR to chromosome 15 in the inbred long-sleep (ILS) × inbred short-sleep (ISS) recombinant inbred panel of mice. This QTL named Fedr2 (fuel efficiency response to DR)-2 modifies body weight (BW) and hair growth (HG) in response to DR. The QTL has been previously mapped using the ISS.Lore5LA (5LA) congenic strain. Here, we have used the reciprocal congenic strain ILS.Lore5SA (5SA) to further investigate Fedr2. The 5LA congenic showed increased ability to maintain BW and HG under DR. For the reciprocal congenic, 5SA, we expected the reciprocal response that the 5SA congenic would have a lesser ability to maintain BW and HG under DR. This expectation was mostly met. The Fedr2S allele conferred lower BW maintenance under DR in both females and males. For females, the difference in BW was significant for the entirety of DR, and for males, the difference became significant at week 17 of DR. For HG, the Fedr2S allele conferred decreased HG ability under DR in males, but not for females. These results highlight the genetic basis for variation in DR response and support the previous observations that Fedr2 mediates BW and HG during DR.