The genetic basis for specific anosmia to isovaleric acid in the mouse

The detection and discrimination of odorants in mammals is thought to be mediated by a family of 100-1000 seven transmembrane domain receptor proteins, although none of these putative olfactory receptors have been shown to bind individual odorants with high affinity. We have used a genetic approach to identify the genomic regions responsible for the differential ability of two inbred mouse strains to detect a single odorant, isovaleric acid. Results obtained with a behavioral assay were consistent with a limited number of genes conferring the ability to detect isovaleric acid. One genetic location mapped to a 0.3 cM region between D4MIT37 and D4MIT156 on mouse chromosome 4. A second locus mapped to the distal end of mouse chromosome 6. The most likely cause of the behavior difference between the two strains of mice is the loss of the receptor protein or proteins responsible for recognizing isovaleric acid. High resolution genetic mapping provides a novel approach to the identification of genes critical for the detection of particular odorants.