Allelic variation of the Tas1r3 taste receptor gene affects sweet taste responsiveness and metabolism of glucose in F₁ Mouse hybrids

In mammals, inter- and intraspecies differences in consumption of sweeteners largely depend on allelic variation of theTas1r3gene (locusSac) encoding the T1R3 protein, a sweet taste receptor subunit. To assess the influence ofTas1r3polymorphisms on feeding behavior and metabolism, we examined the phenotype of F(1)male hybrids obtained from crosses between the following inbred mouse strains: females from 129SvPasCrl (129S2) bearing the recessiveTas1r3allele and males from either C57BL/6J (B6), carrying the dominant allele, or theTas1r3-gene knockout strain C57BL/6J-Tas1r3(tm1Rfm)(B6-Tas1r3-/-). The hybrids 129S2B6F1 and 129S2B6-Tas1r3-/-F1 had identical background genotypes and different sets ofTas1r3alleles. The effect ofTas1r3hemizygosity was analyzed by comparing the parental strain B6 (Tas1r3homozygote) and hemizygous F(1)hybrids B6 x B6-Tas1r3-/-. Data showed that, in 129S2B6-Tas1r3-/-F1 hybrids, the reduction of glucose tolerance, along with lower consumption of and lower preference for sweeteners during the initial licking responses, is due to expression of the recessiveTas1r3allele. Hemizygosity ofTas1r3did not influence these behavioral and metabolic traits. However, the loss of the functionalTas1r3allele was associated with a small decline in the long-term intake and preference for sweeteners and reduction of plasma insulin and body, liver, and fat mass.