Use of the Expanded Panel of BXD Mice Narrow QTL Regions in Ethanol-Induced Locomotor Activation and Motor Incoordination
Article first published online: 7 JUN 2012
Copyright © 2012 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 37, Issue 1, pages 170–183, January 2013
How to Cite
DuBose, C. S., Chesler, E. J., Goldowitz, D. and Hamre, K. M. (2013), Use of the Expanded Panel of BXD Mice Narrow QTL Regions in Ethanol-Induced Locomotor Activation and Motor Incoordination. Alcoholism: Clinical and Experimental Research, 37: 170–183. doi: 10.1111/j.1530-0277.2012.01865.x
- Issue published online: 4 JAN 2013
- Article first published online: 7 JUN 2012
- Manuscript Accepted: 3 APR 2012
- Manuscript Received: 16 AUG 2011
- QTL ;
- Candidate Gene;
- Activity Chamber
Alcohol-related responses are under strong genetic regulation. A wealth of alcohol-related data from recombinant inbred (RI) mouse strains enables genetic correlation and mapping of these traits. Previous studies using RI strains have identified numerous chromosomal locations that underlie differential alcohol sensitivity, although the regions identified are typically large. One means to improve power and precision for genetic analysis is to use a larger genetic reference population. The expanded panel of BXD RI mice was used to identify quantitative trait loci (QTLs) associated with sensitivity to locomotor stimulatory and motor incoordinating effects of alcohol. The goals of this study were to determine whether previously reported QTLs were replicated and refined and to determine whether novel QTLs would be identified.
Following an i.p. dose of 2.25 g/kg of ethanol (EtOH) or saline control, locomotor activation was assessed using an activity chamber and motor incoordination was assessed using the accelerating rotarod. Male and female BXD mice from over 55 strains were tested. Two treatment paradigms were utilized to evaluate the effects of EtOH versus saline treatment-order.
Activity chamber measures showed significant differences in strain, sex, and treatment-order whereas rotarod measures showed significant differences in strain and treatment-order. Significant QTLs for various measures of EtOH-induced locomotor activation were identified on chromosomes 2 and 5 that narrowed QTL regions previously identified from 19 to < 2 Mb. Further, a novel significant QTL for EtOH-induced motor incoordination on chromosome 7 was identified.
Using the expanded RI BXD panel, along with a high precision marker map, several novel QTLs were found and several previously identified QTL regions were confirmed and narrowed. The isogenic nature of the population facilitated detection of treatment-order and sex-specific differences. Smaller QTL regions reduced the number of positional candidates thereby increasing the efficiency with which polymorphisms underlying the QTL will be identified.