title: Use of the expanded panel of BXD mice narrow QTL regions in ethanol-induced locomotor activation and motor incoordination.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA. cdubose3@uthsc.edu
authors.forename: Candis S
authors.initials: CS
authors.lastname: DuBose
authors.forename: Elissa J
authors.initials: EJ
authors.lastname: Chesler
authors.forename: Dan
authors.initials: D
authors.lastname: Goldowitz
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Hamre
mesh_terms: D019973:Alcohol-Related Disorders / Q000235:genetics*; D000818:Animals; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000097:blood; D000431:Ethanol / Q000009:adverse effects* / Q000097:blood; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects* / Q000235:genetics; D040641:Quantitative Trait Loci; D045442:Rotarod Performance Test
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol