PROVISIONAL MAPPING OF QUANTITATIVE TRAIT LOCI FOR CHRONIC ETHANOL WITHDRAWAL SEVERITY IN BXD RECOMBINANT INBRED MICE

Male mice from C57BL/6J (B6), DBA/2J (D2) and their 25 recombinant inb red (RI) strains were exposed to ethanol (EtOH) vapor (3.0-9.0 mg EtOH /liter of air) for 72 hr. Mice were selected such that each strain ave raged 1.34 to 1.59 mg of EtOH/ml of blood on withdrawal. Control group s and EtOH-exposed groups were tested hourly for handling-induced conv ulsions (HIC) for 10 hr and at hr 24 and 25. Strain withdrawal severit y was indexed as the area under the 25-hr HIC curve for the EtOH group minus that strain's equivalent value for the control group. Genome-wi de quantitative trait locus (QTL) analyses correlating strain means wi th allelic status at >1500 markers identified 10 chromosomal regions a t P <.01. These provisionally identified QTLs were on chromosomes 1 (2 QTLs), 3, 9 (2 QTLs), 10, 12, 13, 15 and 18. Multiple regression anal ysis using the four most influential QTLs revealed that these loci con trolled 86% of the genetic variance. A QTL mapped to distal chromosome 1 (P <.001) is in the same region as one previously definitively mapp ed for acute alcohol withdrawal, as well as one mapped for acute pento barbital withdrawal. Several of the QTLs map near potential candidate genes. These provisional linkages will now be confirmed or rejected us ing additional genetically segregating populations.