A COMMON POLYGENIC BASIS FOR QUININE AND PROP AVOIDANCE IN MICE

Inbred strains of mice (Mus musculus) differ greatly in ability to tas te various bitter compounds. For some compounds, the differences resul t from allelic variation at a single locus. However, segregation patte rns incompatible with monogenic inheritance have been found for quinin e avoidance. The Soa bitter sensitivity locus exerts some influence on this phenotype, but an unknown number of other loci also contribute. Relative avoidance patterns for quinine sulfate in panels of naive inb red strains resembled avoidance patterns for 6-n-propyl-2-thiouracil ( PROP), suggesting a common genetic basis. In particular, C57BL/6J mice strongly avoided both 0.1 mM quinine sulfate and 1 mM PROP in two-bot tle preference tests, whereas C3 H/HeJ mice were indifferent to both. Therefore, 12 BXH/Ty recombinant inbred strains, derived from these st rains, were tested with both solutions to begin identification of the unknown bitter loci. Naive mice were tested for four consecutive days with each compound (order counterbalanced). Some BXH/Ty strain means r esembled those of the parent strains, but others were intermediate. Th is indicated recombination among loci affecting avoidance, and therefo re polygenic inheritance. The strain means were highly correlated acro ss compounds (r = 0.98), suggesting that the same polygenes controlled both phenotypes. The BXH/Ty means for both compounds were then compar ed with the strain genotypes at 212 chromosome position markers distri buted throughout the genome. Eight markers on five chromosomes (3, 6, 7, 8 and 9) yielded significant correlations. Six of the markers were correlated with both phenotypes, again suggesting common polygenic inh eritance. The marker with the highest correlation was Prp, tightly lin ked to Soa on chromosome 6. The correlated marker regions likely conta in quantitative trait loci affecting bitter avoidance. The phenotypic similarity of PROP to quinine, rather than to phenylthiourea, apparent ly stemming from a common polygenic basis, indicates a difference betw een mice and humans in gustatory organization related to bitters.