Cocaine, meth response differ between two substrains of 'Black 6' laboratory mouse

December 19, 2013
Separated by more than six decades, the C57BL/6N substrain (left) of laboratory mouse has undergone multiple genetic changes due to spontaneous mutations and is now visibly different from the founder strain, the C57BL/6J of The Jackson Laboratory. Credit: The Jackson Laboratory

Researchers including Jackson Laboratory Professor Gary Churchill, Ph.D., have found a single nucleotide polymorphism (SNP) difference in cocaine and methamphetamine response between two substrains of the C57BL/6 or "Black 6" inbred laboratory mouse, pointing to Cyfip2 as a regulator of cocaine response with a possible role in addiction.

The research team, led by Joseph Takahashi, Ph.D., of University of Texas Southwestern Medical Center and the Howard Hughes Medical Institute, compared the sensitivities to cocaine and methamphetamine in C57BL/6J mice from The Jackson Laboratory and C57BL/6N mice from colonies raised at the National Institutes of Health, finding that 6N mice have lower response than the 6J ones.

Mapping the difference to a single quantitative trail locus (QTL) on chromosome 11, followed by whole-genome sequencing, led to the researchers' identification of a SNP in a gene known as Cyfip2, a highly conserved protein associated with fragile X-mental retardation protein (FMRP), part of a complex that is the most common cause of mental retardation in humans.

The researchers' methods demonstrate that the variations among some 20 C57BL/6 substrains can be used as a rich gene-finding resource. But these variations also highlight the issue of genetic quality control in mouse populations.

Jackson Laboratory founder Clarence Cook Little first developed the C57BL/6 mouse in 1921, and it is now the world's most widely used strain. In 2002 an international consortium published the first genome of a laboratory mouse: that of a 6J mouse from The Jackson Laboratory.

Because of over nearly a century, populations of 6J mice originally obtained from The Jackson Laboratory have developed into at least 20 substrains. Notable among them is the C57BL/6N substrain based on 6J mice that the National Institutes of Health first obtained in 1951. In the intervening decades, the genomes of the substrains have diverged.

"This means that researchers should be very cautious when comparing behavioral data from studies using 6J and 6N strains," Churchill says. "They are clearly not interchangeable."

To address the issue of genetic drift, The Jackson Laboratory uses a genetic quality control program for its most widely used inbred strains, including C57BL/6J. Every five generations, the Laboratory "refreshes" its production colonies by raising from cryopreserved 6J embryos, preventing spontaneous mutations from altering the 6J line.

Explore further: Mouse study links delayed female sexual maturity to longer lifespan

More information: Kumar et al.: C57BL/6N Mutation in Cytoplasmic FMR interacting protein 2 Regulates Cocaine Response. Science, Dec. 20, 2013.

Related Stories

Mouse study links delayed female sexual maturity to longer lifespan

May 7, 2012
An intriguing clue to longevity lurks in the sexual maturation timetable of female mammals, Jackson Laboratory researchers and their collaborators report.

New study solves mouse genome dilemma

May 29, 2011
Laboratory research has always been limited in terms of what conclusions scientists can safely extrapolate from animal experiments to the human population as a whole. Many promising findings in mice have not held up under ...

Recommended for you

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly identified genetic marker may help detect high-risk flu patients

July 17, 2017
Researchers have discovered an inherited genetic variation that may help identify patients at elevated risk for severe, potentially fatal influenza infections. The scientists have also linked the gene variant to a mechanism ...

Newly discovered gene variants link innate immunity and Alzheimer's disease

July 17, 2017
Three new gene variants, found in a genome wide association study of Alzheimer's disease (AD), point to the brain's immune cells in the onset of the disorder. These genes encode three proteins that are found in microglia, ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

davidivad
not rated yet Dec 19, 2013
the question here is whether or not getting a retarded mouse high improves its quality of life.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.