NIAAA-led study verifies environment-dependent behavioral variation in genetically identical mice

June 03, 1999

John Crabbe, Ph.D., Portland Veterans Affairs Medical Center and Oregon Health Sciences University, Department of Behavioral Neuroscience, with colleagues in three widely separated laboratories report in this week's Science that animals with the same genes performed differently on a variety of behavioral tests depending on the animals' location. This was true although a long list of environmental influences was equalized among the three sites.

"The conclusion that unknown, subtle environmental features have profound effects on the behaviors of isogenic animals reinforces the idea that, for behaviors like alcoholism, genes will define risk, not destiny," said NIAAA Director Enoch Gordis, M.D. As one of 15 U.S. sites for interdisciplinary research on certain aspects of alcohol disorders and alcohol-related problems, the NIAAA-supported Alcohol Research Center at Portland, directed by Dr. Crabbe, focuses on genetic determinants of neuroadaptation to alcohol.

"Behaviors known to be strongly genetically influenced, such as alcohol preference in C57BL/6J and alcohol avoidance in DBA/2J mice, were least susceptible to site-specific environmental effects, " said Dr. Crabbe. "More susceptible were behaviors with smaller genetic effects, especially behavioral effects thought to be the result of a single gene knockout."

Dr. Crabbe's laboratory and laboratories at the University of Alberta in Edmonton, Alberta, Canada, and the State University of New York at Albany confirmed a long-held assumption among scientists that tests of genetically influenced mouse behaviors are affected by the laboratories in which they are studied. Researchers traditionally have tried to mitigate these effects by repeating an experiment at multiple sites.

Dr. Crabbe and his colleagues conclude that for small genetic effects, especially those believed to be the result of a single gene mutation, researchers should replicate tests locally, then conduct multiple tests of a single behavioral domain (e.g., multiple tests of anxiety-related behavior) in multiple laboratories. It is not clear that standardization of behavioral tests across laboratories improves matters, write the authors.

For the current study, Dr. Crabbe and his colleagues simultaneously administered six behavioral tests using seven genetic mouse strains and a mutant strain that lacks a single neurotransmitter receptor gene. Apparatus, test protocols, and many aspects of animal husbandry were standardized across sites.

While results for some behavioral tests were consistent across the three labs, other test results showed significant environmental differences. Individual mouse strains also performed differently depending on where they were tested, with the mutant strain evidencing the greatest degree of difference at the separate sites.

"Our hope is to generate discussion and then action to identify and reduce individual laboratory influences," Dr. Crabbe said. "Only after site-specific environmental influences are accounted for can scientists conclude that a specific gene influences a specific behavioral domain."

The Office of Behavioral and Social Sciences Research, National Institutes of Health, supported the study through supplements to grants by the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse. NIH is the Nation's lead agency for biomedical and behavioral research. For additional alcohol research information and publications, visit

NIH/National Institute on Alcohol Abuse and Alcoholism

Related Alcohol Articles from Brightsurf:

Alcohol use changed right after COVID-19 lockdown
One in four adults reported a change in alcohol use almost immediately after stay-at-home orders were issued: 14% reported drinking more alcohol and reported higher levels of stress and anxiety than those who did not drink and those whose use stayed the same.

Changes in hospitalizations for alcohol use disorder in US
Changes over nearly two decades in the rate of hospitalizations and in-hospital deaths from alcohol use disorder in the US were examined in this study.

Associations of alcohol consumption, alcohol-induced passing out with risk of dementia
The risk of future dementia associated with overall alcohol consumption and alcohol-induced loss of consciousness in a population of current drinkers was examined in this observational study with more than 131,000 adults.

New alcohol genes uncovered
Do you have what is known as problematic alcohol use?

Does estrogen influence alcohol use disorder?
A new study from researchers at the University of Illinois at Chicago shows that high estrogen levels may make alcohol more rewarding to female mice.

Sobering new data on drinking and driving: 15% of US alcohol-related motor vehicle fatalities involve alcohol under the legal limit
A new study in the American Journal of Preventive Medicine, published by Elsevier, found that motor vehicle crashes involving drivers with blood alcohol concentrations (BACs) below the legal limit of 0.08 percent accounted for 15% of alcohol-involved crash deaths in the United States.

Alcohol-induced deaths in US
National vital statistics data from 2000 to 2016 were used to examine how rates of alcohol-induced deaths (defined as those deaths due to alcohol consumption that could be avoided if alcohol weren't involved) have changed in the US and to compare the results by demographic groups including sex, race/ethnicity, age, socioeconomic status and geographic location.

Cuts in alcohol duty linked to 2000 more alcohol-related deaths in England
Government cuts to alcohol taxes have had dramatic consequences for public health, including nearly 2000 more alcohol-related deaths in England since 2012, according to new research from the University of Sheffield's School of Health and Related Research (ScHARR).

Integrated stepped alcohol treatment for people in HIV care improves both HIV & alcohol outcomes
Increasing the intensity of treatment for alcohol use disorder (AUD) over time improves alcohol-related outcomes among people with HIV, according to new clinical research supported by the National Institutes of Health.

The Lancet:Targets to reduce harmful alcohol use are likely to be missed as global alcohol intake increases
Increasing rates of alcohol use suggest that the world is not on track to achieve targets against harmful alcohol use, according to a study of 189 countries' alcohol intake between 1990-2017 and estimated intake up to 2030, published in The Lancet.

Read More: Alcohol News and Alcohol Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to