Genetic controls of Tas1r3 -independent sucrose consumption in mice

We have previously used crosses between C57BL/6ByJ (B6) and 129P3/J (129) inbred strains to map a quantitative trait locus (QTL) on mouse chromosome (Chr) 4 that affects behavioral and neural responses to sucrose. We have named it the sucrose consumption QTL 2 ( Scon2 ), and shown that it corresponds to the Tas1r3 gene , which encodes a sweet taste receptor subunit TAS1R3. To discover other sucrose consumption QTLs, we have intercrossed B6 inbred and 129.B6- Tas1r3 congenic mice to produce F 2 hybrids, in which Scon2 ( Tas1r3 ) does not segregate, and hence does not contribute to phenotypical variation. Chromosome mapping using this F 2 intercross identified two main-effect QTLs, Scon3 (Chr9) and Scon10 (Chr14), and an epistatically interacting QTL pair Scon3 (Chr9)– Scon4 (Chr1). Using serial backcrosses, congenic and consomic strains, we conducted high-resolution mapping of Scon3 and Scon4 and analyzed their epistatic interactions. We used mice with different Scon3 or Scon4 genotypes to understand whether these two QTLs influence sucrose intake via gustatory or postoral mechanisms. These studies found no evidence for involvement of the taste mechanisms, but suggested involvement of energy metabolism. Mice with the B6 Scon4 genotype drank less sucrose in two-bottle tests, and also had a higher respiratory exchange ratio and lower energy expenditure under basal conditions (when they had only chow and water available). Our results provide evidence that Scon3 and Scon4 influence mouse-to-mouse variation in sucrose intake and that both likely act through a common postoral mechanism.