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Genetics of mouse behavioral and peripheral neural responses to sucrose

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Abstract

Mice of the C57BL/6ByJ (B6) strain have higher consumption of sucrose, and stronger peripheral neural responses to it, than do mice of the 129P3/J (129) strain. To identify quantitative trait loci (QTLs) responsible for this strain difference and to evaluate the contribution of peripheral taste responsiveness to individual differences in sucrose intake, we produced an intercross (F2) of 627 mice, measured their sucrose consumption in two-bottle choice tests, recorded the electrophysiological activity of the chorda tympani nerve elicited by sucrose in a subset of F2 mice, and genotyped the mice with DNA markers distributed in every mouse chromosome. We confirmed a sucrose consumption QTL (Scon2, or Sac) on mouse chromosome (Chr) 4, harboring the Tas1r3 gene, which encodes the sweet taste receptor subunit TAS1R3 and affects both behavioral and neural responses to sucrose. For sucrose consumption, we also detected five new main-effect QTLs, Scon6 (Chr2), Scon7 (Chr5), Scon8 (Chr8), Scon3 (Chr9), and Scon9 (Chr15), and an epistatically interacting QTL pair Scon4 (Chr1) and Scon3 (Chr9). No additional QTLs for the taste nerve responses to sucrose were detected besides Scon2 (Tas1r3) on Chr4. Identification of the causal genes and variants for these sucrose consumption QTLs may point to novel mechanisms beyond peripheral taste sensitivity that could be harnessed to control obesity and diabetes.

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Acknowledgements

We gratefully acknowledge Maria L. Theodorides, Zakiyyah Smith, Mauricio Avigdor, and Amy Colihan for assistance with animal breeding. We also acknowledge Richard Copeland and the consistent high-quality assistance of the Animal Care Staff at the Monell Chemical Senses Center and thank them for their service.

Funding

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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Author notes

  1. Xia Li

    Present address: Sonora Quest Laboratories, Phoenix, AZ, USA

  2. Yutaka Ishiwatari

    Present address: Ajinomoto Co., Inc., Tokyo, Japan

  3. Alexander A. Bachmanov

    Present address: GlaxoSmithKline, Collegeville, PA, USA

Authors and Affiliations

  1. Monell Chemical Senses Center, Philadelphia, PA, USA

    Cailu Lin, Masashi Inoue, Xia Li, Natalia P. Bosak, Yutaka Ishiwatari, Michael G. Tordoff, Gary K. Beauchamp, Alexander A. Bachmanov & Danielle R. Reed

  2. Laboratory of Cellular Neurobiology, School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo, Japan

    Masashi Inoue

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  1. Cailu Lin
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Contributions

AAB, DRR, MGT, and GKB designed the study. AAB bred and phenotyped mice. MI conducted electrophysiological experiments. CL, XL, NPB, and YI genotyped mice. CL, YI, AAB, and DRR analyzed data. CL and DRR wrote the paper. AAB, MGT, and GKB commented and edited the paper. All authors read the paper and approved its contents.

Corresponding authors

Correspondence to Alexander A. Bachmanov or Danielle R. Reed.

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Conflict of interest

On behalf of all authors, the corresponding author states that there are no conflicts of interest.

Ethical approval

All animal procedures in this study were approved by the Institutional Animal Care and Use Committee of the Monell Chemical Senses Center.

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Accession IDs: MGI:2661414 (Scon2), MGI:3783324 (Scon3), MGI:5489743 (Scon4), MGI:6451653 (Scon6), MGI:6451654 (Scon7), MGI:6451655 (Scon8), MGI:6451656 (Scon9).

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Lin, C., Inoue, M., Li, X. et al. Genetics of mouse behavioral and peripheral neural responses to sucrose. Mamm Genome 32, 51–69 (2021). https://doi.org/10.1007/s00335-021-09858-4

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