Genetic Controls of Tas1r3-independent Sucrose Consumption in Mice

Overview

Journal Mamm Genome

Specialty Genetics

Date 2021 Mar 12

PMID 33710367

Authors

Cailu Lin

Michael G Tordoff

Xia Li

Natalia P Bosak

Masashi Inoue

Yutaka Ishiwatari

Longhui Chen

Gary K Beauchamp

Alexander A Bachmanov

Danielle R Reed

Affiliations

Soon will be listed here.

Abstract

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 hybrids, in which Scon2 (Tas1r3) does not segregate, and hence does not contribute to phenotypical variation. Chromosome mapping using this F 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.

References

Alexandre-Gouabau M, Bailly E, Moyon T, Grit I, Coupe B, Le Drean G . Postnatal growth velocity modulates alterations of proteins involved in metabolism and neuronal plasticity in neonatal hypothalamus in rats born with intrauterine growth restriction. J Nutr Biochem. 2011; 23(2):140-52. DOI: 10.1016/j.jnutbio.2010.11.008. View

Ayala J, Samuel V, Morton G, Obici S, Croniger C, Shulman G . Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice. Dis Model Mech. 2010; 3(9-10):525-34. PMC: 2938392. DOI: 10.1242/dmm.006239. View

Bachmanov A, Bosak N, Floriano W, Inoue M, Li X, Lin C . Genetics of sweet taste preferences. Flavour Fragr J. 2011; 26(4):286-294. PMC: 3130742. DOI: 10.1002/ffj.2074. View

Bachmanov A, Li X, Reed D, Ohmen J, Li S, Chen Z . Positional cloning of the mouse saccharin preference (Sac) locus. Chem Senses. 2001; 26(7):925-33. PMC: 3644801. DOI: 10.1093/chemse/26.7.925. View

Bachmanov A, Reed D, Ninomiya Y, Inoue M, Tordoff M, Price R . Sucrose consumption in mice: major influence of two genetic loci affecting peripheral sensory responses. Mamm Genome. 1997; 8(8):545-8. PMC: 3638219. DOI: 10.1007/s003359900500. View

Bachmanov A, Reed D, Tordoff M, Price R, Beauchamp G . Intake of ethanol, sodium chloride, sucrose, citric acid, and quinine hydrochloride solutions by mice: a genetic analysis. Behav Genet. 1996; 26(6):563-73. PMC: 3661408. DOI: 10.1007/BF02361229. View

Bachmanov A, Reed D, Tordoff M, Price R, Beauchamp G . Nutrient preference and diet-induced adiposity in C57BL/6ByJ and 129P3/J mice. Physiol Behav. 2001; 72(4):603-13. PMC: 3341942. DOI: 10.1016/s0031-9384(01)00412-7. View

Bachmanov A, Tordoff M, Beauchamp G . Ethanol consumption and taste preferences in C57BL/6ByJ and 129/J mice. Alcohol Clin Exp Res. 1996; 20(2):201-6. PMC: 3638218. DOI: 10.1111/j.1530-0277.1996.tb01630.x. View

Bachmanov A, Tordoff M, Beauchamp G . Sweetener preference of C57BL/6ByJ and 129P3/J mice. Chem Senses. 2001; 26(7):905-13. PMC: 3718299. DOI: 10.1093/chemse/26.7.905. View

10.

Barrett T, Wilhite S, Ledoux P, Evangelista C, Kim I, Tomashevsky M . NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res. 2012; 41(Database issue):D991-5. PMC: 3531084. DOI: 10.1093/nar/gks1193. View

11.

Baumeier C, Kaiser D, Heeren J, Scheja L, John C, Weise C . Caloric restriction and intermittent fasting alter hepatic lipid droplet proteome and diacylglycerol species and prevent diabetes in NZO mice. Biochim Biophys Acta. 2015; 1851(5):566-76. DOI: 10.1016/j.bbalip.2015.01.013. View

12.

Blizard D, Kotlus B, Frank M . Quantitative trait loci associated with short-term intake of sucrose, saccharin and quinine solutions in laboratory mice. Chem Senses. 1999; 24(4):373-85. DOI: 10.1093/chemse/24.4.373. View

13.

Blizard D, McClearn G . Association between ethanol and sucrose intake in the laboratory mouse: exploration via congenic strains and conditioned taste aversion. Alcohol Clin Exp Res. 2000; 24(3):253-8. View

14.

Broman K, Wu H, Sen S, Churchill G . R/qtl: QTL mapping in experimental crosses. Bioinformatics. 2003; 19(7):889-90. DOI: 10.1093/bioinformatics/btg112. View

15.

Buresh R, Kuslak S, Rusch M, Vezina C, Selleck S, Marker P . Sulfatase 1 is an inhibitor of ductal morphogenesis with sexually dimorphic expression in the urogenital sinus. Endocrinology. 2010; 151(7):3420-31. PMC: 2903932. DOI: 10.1210/en.2009-1359. View

16.

Chen J, Bardes E, Aronow B, Jegga A . ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res. 2009; 37(Web Server issue):W305-11. PMC: 2703978. DOI: 10.1093/nar/gkp427. View

17.

Choi Y, Chan A . PROVEAN web server: a tool to predict the functional effect of amino acid substitutions and indels. Bioinformatics. 2015; 31(16):2745-7. PMC: 4528627. DOI: 10.1093/bioinformatics/btv195. View

18.

Darvasi A, Soller M . Advanced intercross lines, an experimental population for fine genetic mapping. Genetics. 1995; 141(3):1199-207. PMC: 1206841. DOI: 10.1093/genetics/141.3.1199. View

19.

Dutta S, Sengupta P . Men and mice: Relating their ages. Life Sci. 2015; 152:244-8. DOI: 10.1016/j.lfs.2015.10.025. View

20.

Fuller J . Single-locus control of saccharin preference in mice. J Hered. 1974; 65(1):33-6. DOI: 10.1093/oxfordjournals.jhered.a108452. View