COMMON GENETIC-DETERMINANTS OF THE ATAXIC AND HYPOTHERMIC EFFECTS OF ETHANOL IN BXD TY RECOMBINANT INBRED MICE - GENETIC CORRELATIONS AND QUANTITATIVE TRAIT LOCI/

Sensitivity and tolerance to ethanol-induced ataxia and hypothermia ar e determined in part by genetic factors; some genes that affect one of these traits may affect others as well. To test this general hypothes is, we examined hypothermia and two tests of ataxia in the C57BL/6J an d DBA/2J inbred mouse strains and in 18 to 25 of their recombinant inb red strains. Genetic correlations among strain mean responses revealed strong positive associations of genetic origin between sensitivity an d tolerance for each of the three responses. Furthermore, tolerance to grid test ataxia and tolerance to hypothermia were positively associa ted. Sensitivity scores across the three responses were uncorrelated. The second method employed to assess genetic correlation was to examin e the pattern of genetic locations of quantitative trait loci (QTLs) p rovisionally identified using genetic mapping procedures. This method identified 3 to 14 QTLs associated with each trait. Within each respon se, a number of these associations were in common for measures of sens itivity and tolerance; this suggests the existence of several specific genes that exert pleiotropic effects on sensitivity and tolerance. In a result consistent with the analyses of genetic correlations, there was modest evidence for QTLs associated across measures. Some QTLs ass ociated with multiple traits mapped to chromosomal regions where candi date genes (e.g., genes for neurotransmitter receptors) have been mapp ed. In summary, the analyses presented suggest modest commonality of g enetic influence on tolerance to some measures of ataxia and hypotherm ia, and they strongly support previous data indicating that sensitivit y and tolerance to specific effects of ethanol share common genetic de terminants.