International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSITIONAL CLONING OF THE MOUSE SACCHARIN PREFERENCE (SAC) LOCUS

Alexander Bachmanov
Monell Chemical Senses Center
3500 Market Street
Philadelphia, PA 19104 USA

Co-Authors: 1)Li X, 1)Reed DR, 2)Ohmen JD, 1)Li S, 1)Chen Z, 1)Tordoff MG, 2&3)de Jong PJ, 2)Wu C, 2)West DB, 2)Chatterjee A, 2)Ross DA, 1&4)Beauchamp GK
Institutions: 1)Monell Chemical Senses Center, 2)Pfizer Global Research and Development, 3)Children's Hospital Oakland Research Institute, 4)University of Pennsylvania

Differences in sweetener intake among inbred strains of mice are partially determined by allelic variation of the saccharin preference (Sac) locus. Genetic and physical mapping limited a critical genomic interval containing Sac to a 194-kb DNA fragment. Sequencing and annotation of this region identified a gene (Tas1r3) encoding the third member of the T1R family of putative taste receptors, T1R3. Introgression by serial backcrossing of the 194-kb chromosomal fragment containing the Tas1r3 allele from the high-sweetener preferring C57BL/6ByJ strain onto the genetic background of the low-sweetener preferring 129P3/J strain rescued its low sweetener preference phenotype. 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. 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. This study provides compelling evidence that Tas1r3 is equivalent to the Sac locus and that the T1R3 receptor responds to sweeteners.


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