Distinct Roles for Two Chromosome 1 Loci in Ethanol Withdrawal, Consumption, and Conditioned Place Preference.

We previously identified a region on chromosome 1 that harbor quantitative trait loci (QTLs) with large effects on alcohol withdrawal risk using both chronic and acute models in mice. Here, using newly created and existing QTL interval-specific congenic (ISC) models, we report the first evidence that this region harbors two distinct alcohol withdrawal QTLs (and ), which underlie 13% and 3-6%, respectively, of the genetic variance in alcohol withdrawal severity measured using the handling-induced convulsion. Our results also precisely localize and to discreet chromosome regions (syntenic with human 1q23.

A Systems Approach Implicates a Brain Mitochondrial Oxidative Homeostasis Co-expression Network in Genetic Vulnerability to Alcohol Withdrawal.

Genetic factors significantly affect vulnerability to alcohol dependence (alcoholism). We previously identified quantitative trait loci on distal mouse chromosome 1 with large effects on predisposition to alcohol physiological dependence and associated withdrawal following both chronic and acute alcohol exposure in mice (, respectively). We fine-mapped these loci to a 1.

Discovering genes involved in alcohol dependence and other alcohol responses: role of animal models.

The genetic determinants of alcoholism still are largely unknown, hindering effective treatment and prevention. Systematic approaches to gene discovery are critical if novel genes and mechanisms involved in alcohol dependence are to be identified. Although no animal model can duplicate all aspects of alcoholism in humans, robust animal models for specific alcohol-related traits, including physiological alcohol dependence and associated withdrawal, have been invaluable resources.

Interval-specific congenic animals for high-resolution quantitative trait loci mapping.

Behavioral phenotypes (e.g., drug responses and withdrawal) are typically quantitative traits-characteristics that differ along a spectrum in the extent to which an individual possesses that characteristic.