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 F2 hybrids, in which Scon2 (Tas1r3) does not segregate, and hence does not contribute to phenotypical variation. Chromosome mapping using this F2 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.
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We gratefully acknowledge Maria L. Theodorides, Zakiyyah Smith, Mauricio Avigdor, and Amy Colihan for assistance with animal breeding. We also acknowledge Richard Copeland and Nettie Carter-Lischka for the consistent high-quality assistance of the animal care staff at the Monell Chemical Senses Center and thank them for their service. Matt Kirkey assisted with genotyping the congenic mice. Anthony Sclafani made constructive comments on an earlier draft of the manuscript.
National Institutes of Health grants R01 DC00882 (AAB and GKB), R01 AA11028 (AAB and MGT), R03 DC03854, R03 TW007429 (AAB), R03 DC03509, R01 DC04188, R01 DK55853, R01 DK094759, R01 DK058797, P30 DC011735, S10 OD018125, S10 RR025607, S10 RR026752, and G20 OD020296 (DRR) and institutional funds from the Monell Chemical Senses Center supported this work, including genotyping and the purchase of equipment. The Center for Inherited Disease Research through the auspices of the National Institutes of Health provided genotyping services.
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On behalf of all authors, the corresponding author states that there are no conflict of interest.
All animal study procedures were approved by the Monell Chemical Senses Center Institutional Care and Use Committee.
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MGI:3783324 (Scon3), MGI:5489743 (Scon4), MGI:6451657 (Scon10), MMRRC:036684-JAX (129P3/J-Chr 1C57BL6ByJ/MonMmjax), MMRRC:036687-JAX (129P3/J-Chr 9C57B6/ByJ/ MonMmjax), MMRRC:036690-JAX (C57BL/6ByJ-Chr 9129P3/J/ MonMmjax).
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Lin, C., Tordoff, M.G., Li, X. et al. Genetic controls of Tas1r3-independent sucrose consumption in mice. Mamm Genome 32, 70–93 (2021). https://doi.org/10.1007/s00335-021-09860-w