Taste dysfunction in BTBR mice due to a mutation of Itpr3, the inositol triphosphate receptor 3 gene

Physiol Genomics. 2013 Sep 16;45(18):834-55. doi: 10.1152/physiolgenomics.00092.2013. Epub 2013 Jul 16.

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.

Keywords: NZW/LacJ; QTL; bitter; sweet; umami.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Body Weight
  • Choice Behavior
  • Crosses, Genetic
  • Feeding Behavior
  • Female
  • Gene Deletion
  • Genotype
  • Haplotypes
  • Inositol 1,4,5-Trisphosphate Receptors / genetics*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Knockout
  • Mutation*
  • Phenotype
  • Receptors, G-Protein-Coupled / metabolism
  • Sequence Analysis, DNA
  • Taste / genetics*
  • Taste / physiology
  • Time Factors

Substances

  • ITPR3 protein, mouse
  • Inositol 1,4,5-Trisphosphate Receptors
  • Receptors, G-Protein-Coupled