Disease relevance of Tas1r3

• Virions from Sac- cells, which contained 100% 90K E2, fused L2 cells rapidly without requiring virus replication, whereas virions from 17 Cl 1 cells, which had 50% 90K E2, required trypsin activation to induce rapid fusion (Sturman et al., J. Virol. 56:904-911, 1985) [1].
• Mice infected with lactate dehydrogenase-elevating virus (LDV) developed antibodies reactive with a tumour cell surface antigen (TSA) of Moloney sarcoma virus (Mo-MSV)-transformed mouse cells (Sac) [2].
• Hybridomas producing anti-46K antibodies were established by fusion of mouse myeloma cells with spleen cells taken from mice bearing Sac tumour cells infected with Moloney helper virus [3].

Psychiatry related information on Tas1r3

• Based upon the results of these studies, we conclude that polymorphisms in the protein-coding regions of the sweet receptor gene Tas1r3 are uncommon and do not account for individual differences in saccharin preference for these strains of rats [4].
• To psychophysically examine whether these phenotypes are due to sensory sensitivity as opposed to hedonic responsiveness, we measured taste signal detection of sucrose, glucose, and glycine by Sac taster (C57BL/6J and SWR/J) and non-taster (129P3/J and DBA/2J) strains in an operant conditioning paradigm using a gustometer [5].

High impact information on Tas1r3

• The Sac locus in mouse, mapped to the distal end of chromosome 4 (refs. 7-9), is the major determinant of differences between sweet-sensitive and -insensitive strains of mice in their responsiveness to saccharin, sucrose and other sweeteners [6].
• To identify the human Sac locus, we searched for candidate genes within a region of approximately one million base pairs of the sequenced human genome syntenous to the region of Sac in mouse [6].
• According to models of its structure, T1r3 from non-tasters is predicted to have an extra amino-terminal glycosylation site that, if used, would interfere with dimerization [6].
• In addition, a perfect correlation exists between two different T1r3 alleles and Sac phenotypes in recombinant inbred mouse strains [7].
• The transforming activities of DNAs of all five MMTV-induced tumors, the chemical carcinogen-induced mouse tumor, and the human tumor cell line were inactivated by digestion with the restriction endonucleases Pvu II and Sac I, but not by BamHI, EcoRI, HindIII, Kpn I, or Xho I [8].

Chemical compound and disease context of Tas1r3

• Monoclonal antibodies were raised against a cell surface glycoprotein (46K antigen) expressed by a Moloney sarcoma virus (Mo-MSV)-transformed STU mouse cell line (Sac) [3].

Biological context of Tas1r3

• Polymorphisms of Tas1r3 that are likely to have functional significance were identified using analysis of genomic sequences and sweetener-preference phenotypes of genealogically distant mouse strains [9].
• Tas1r3 has two common haplotypes, consisting of six single nucleotide polymorphisms: one haplotype was found in mouse strains with elevated sweetener preference and the other in strains relatively indifferent to sweeteners [9].
• We conclude that cat Tas1r3 is an apparently functional and expressed receptor but that cat Tas1r2 is an unexpressed pseudogene [10].
• Molecular genetics and heterologous expression implicate T1r2 plus T1r3 as a sweet-responsive receptor,and T1r1 plus T1r3,as well as a truncated form of the type 4 metabotropic glutamate receptor (taste-mGluR4),as umami-responsive receptors [11].
• Possible effects of these intronic nucleotide variants on Tas1r3 gene expression or the presence of T1R3 protein in taste papillae were evaluated in the ACI and FH/Wjd strains [4].

Anatomical context of Tas1r3

• In situ hybridization and immunohistochemical studies demonstrate that Tas1r3 is expressed, as expected, in taste buds [10].
• Taste enhancing effects of sodium saccharin (Sac) on responses to particular sweet-tasting D-amino acids were found during the recording of mouse chorda tympani nerve responses to various taste stimuli in C57BL and BALB strains [12].
• Using transgenic mice expressing enhanced green fluorescent protein under the control of the Trpm5 promoter, we found colocalization of Trpm5 and alpha-gustducin in tufted cells at the surface epithelium of the colon, but these cells did not express T1r3 or PLCbeta2 [13].
• The majority of the Sac-cells became involved in syncytium formation [14].
• The sarcoma-helper virus complex released from AP 129 infected Sac-cells led to transformation of cultured cells from different mammalian species (mink, goat, dog) [14].

Associations of Tas1r3 with chemical compounds

• We asked how Tas1r3 polymorphisms influence the initial licking responses of four T strains (FVB/NJ, SWR/J, SM/J, and C57BL/6J) and four NT strains (BALB/cJ, 129P3/J, DBA/2J, and C3H/HeJ) to two sweeteners (sucrose and SC-45647, an artificial sweetener) [15].
• We measured Tas1r3 gene expression, transcript size, and T1R3 immunoreactivity in the taste tissue of two inbred mouse strains with different Tas1r3 haplotypes and saccharin preferences [16].
• Stimulus processing of glycine is dissociable from that of sucrose and glucose based on behaviorally measured taste signal detection in Sac 'taster' and 'non-taster' mice [5].
• Except for Sac, various sweet-tasting amino acids and sugars and NaCl also tested showed no enhancing effect on D-phenylalanine responses in C57BL mice [12].
• In both strains, responses to D-tryptophan and D-histidine significantly increased (167.7-216.7% of control) after the stimulation with Sac as compared with those applied before Sac [12].

Other interactions of Tas1r3

• The Gpr70 gene maps proximal to Sac, which demonstrates that they are different loci [17].
• For chorda tympani responses, significant linkages to Tas1r3 were found for the sweeteners sucrose, saccharin, D-phenylalanine, D-tryptophan, and SC-45647 but not glycine, L-proline, L-alanine, or L-glutamine [18].
• The present experiment illustrates the utility of a 6 h fluid intake test in the mapping of Sac and Qui loci [19].
• We found a large degree of colocalization of Trpm5, alpha-gustducin, T1r1, and T1r3 in tufted cells of the duodenal villi, but these cells rarely expressed PLCbeta2 [13].
• The sweetness tasting gene Sac has been mapped to chromosome 4 at 8.1 +/- 3.4 cM distal to Nppa (formerly Pnd) [20].

Analytical, diagnostic and therapeutic context of Tas1r3

• Message from Tas1r3 was detected by RT-PCR of taste tissue [10].
• Genetic mapping of T1R3 with a mouse/hamster radiation hybrid panel located the gene on the distal end of mouse chromosome 4 correlated with the Sac locus affecting sweet sensitivity of mice [21].
• Only transplantation of helper virus-superinfected Sac cells led to the development of anti-46K antibodies in addition to antibodies against helper virus structural antigens [3].
• The number of cells expressing T1r3, gustducin, Mash1 and Nkx2.2 gradually decreased after denervation [22].

References