title: Taste dysfunction in BTBR mice due to a mutation of Itpr3, the inositol triphosphate receptor 3 gene.
abstract: The BTBR T+ tf/J (BTBR) mouse strain is indifferent to exemplars of sweet, Polycose, umami, bitter, and calcium tastes, which share in common transduction by G protein-coupled receptors (GPCRs). To investigate the genetic basis for this taste dysfunction, we screened 610 BTBR×NZW/LacJ F2 hybrids, identified a potent QTL on chromosome 17, and isolated this in a congenic strain. Mice carrying the BTBR/BTBR haplotype in the 0.8-Mb (21-gene) congenic region were indifferent to sweet, Polycose, umami, bitter, and calcium tastes. To assess the contribution of a likely causative culprit, Itpr3, the inositol triphosphate receptor 3 gene, we produced and tested Itpr3 knockout mice. These were also indifferent to GPCR-mediated taste compounds. Sequencing the BTBR form of Itpr3 revealed a unique 12 bp deletion in Exon 23 (Chr 17: 27238069; Build 37). We conclude that a spontaneous mutation of Itpr3 in a progenitor of the BTBR strain produced a heretofore unrecognized dysfunction of GPCR-mediated taste transduction.
authors.affiliation: Monell Chemical Senses Center, Philadelphia, Pennsylvania.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Tordoff
authors.forename: Hillary T
authors.initials: HT
authors.lastname: Ellis
mesh_terms: D000818:Animals; D001835:Body Weight; D002755:Choice Behavior; D003433:Crosses, Genetic; D005247:Feeding Behavior; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006239:Haplotypes; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D009154:Mutation; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013649:Taste / Q000235:genetics* / Q000502:physiology; D013997:Time Factors
chemical_list: C582634:ITPR3 protein, mouse; D053496:Inositol 1,4,5-Trisphosphate Receptors; D043562:Receptors, G-Protein-Coupled
keywords: NZW/LacJ; QTL; bitter; sweet; umami