Quantitative trait loci mapping of genes that influence the sensitivity and tolerance to ethanol-induced hypothermia in BXD recombinant inbred mice.
A recent method allows the identification of the rough genetic map location in mice of genes that exert modest effects on continuously distributed (i.e., quantitative) variables. Sensitivity and tolerance tolerance to the hypothermic effect of ethanol were studied with the purpose of identifying such quantitative trait loci (QTL). Mice from two progenitor inbred strains, C57BL/6J and DBA/2J, and 19 of their recombinant inbred (RI) BXD strains, were given ethanol daily for 3 days. By administering several doses of ethanol and recording multiple postdrug temperatures on the first and third injection day, the authors were able to compute several indices of initial sensitivity and tolerance magnitude in the RI strain battery. The strains differed at most times and doses in their acute reductions in body temperature with respect to their predrug base lines, which indicated genetic control of sensitivity to ethanol-induced hypothermia. The areas under the curve (which describes the initial hypothermic response over time), a measure that reflects both the maximal hypothermia achieved and the duration of total hypothermic response, also differed. The strains also differed in the magnitude of the tolerance developed to ethanol-induced hypothermia. Genetic determinants of sensitivity (and tolerance) to different doses of ethanol were primarily independent, although genetic sensitivity and tolerance to the intermediate (2- and 3-g/kg) doses were significantly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)
Crabbe
J C
JC
Research Service, VA Medical Center, Portland, Oregon.
Belknap
J K
JK
Mitchell
S R
SR
Crawshaw
L I
LI
D000818:Animals; D002874:Chromosome Mapping; D004361:Drug Tolerance; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D007035:Hypothermia / Q000139:chemically induced* / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D011110:Polymorphism, Genetic; D012680:Sensitivity and Specificity
D005819:Genetic Markers; D000431:Ethanol