Taste sensitivity to a mixture of monosodium glutamate and inosine 5′monophosphate by mice lacking both subunits of the T1R1+T1R3 amino acid receptor

The taste of L-glutamate and its synergism with 5'-ribonucleotides is thought to be primarily mediated through the T1R1+T1R3 heterodimer in some mammals, including rodents and humans. While knockout (KO) mice lacking either receptor subunit show impaired sensitivity to a range of monosodium glutamate (MSG) concentrations mixed with 2.5 mM inosine 5'-monophosphate (IMP) in amiloride, wild-type (WT) controls can detect this IMP concentration, hindering direct comparison between genotypes. Moreover, some residual sensitivity persists in the KO group, suggesting that the remaining subunit could maintain a limited degree of function. Here, C57BL/6J, 129X1/SvJ, and TIR1+T1R3 double KO mice (n = 16 each to start the experiment) were trained in a two-response operant task in gustometers and then tested for their ability to discriminate 100 mu M amiloride from MSG (starting with 0.6 M) and IMP (starting with 2.5 mM) in amiloride (MSG+I+ A). Testing continued with successive dilutions of both MSG and IMP (in amiloride). The two WT strains were similarly sensitive to MSG+I+ A (P > 0.8). KO mice, however, were significantly impaired relative to either WT strain (P < 0.01), although they were able to detect the highest concentrations. Thus, normal detectability of MSG +I+ A requires an intact TIR1+T1R3 receptor, without regard for allelic variation in the T1R3 gene between the WT strains. Nevertheless, residual sensitivity by the T1R1+T1R3 KO mice demonstrates that a T1R-independent mechanism can contribute to the detectability of high concentrations of this prototypical umami compound stimulus.