Common Lab Mice Differ

Related substrains of the Black 6 lab mouse carry key genetic polymorphisms, including one that has a dramatic effect on the rodents’ responses to cocaine.

By Jef Akst | January 8, 2014

WIKIMEDIA, RAMAThe Black 6 mouse strain is the most commonly used lab mouse in the United States, and its highly inbred nature has led scientists to believe that closely related strains are just that, harboring very few genetic differences. But a study published last month (December 20) in Science suggested that not only do mice of Black 6 substrains differ at the level of their DNA, but that those genetic variations can translate into some fairly significant behavioral differences.

Specifically, Joseph Takahashi of the University of Texas Southwestern Medical Center in Dallas and his colleagues compared mice of the C57BL/6J strain, which serves as the reference for the mouse genome sequence as well as several behavioral and physiological phenotypes, with animals of the related C57BL/6N substrain, which yielded the embryonic stem cell line used by the International Knockout Mouse Consortium to establish a library of mouse embryos missing different genes. The researchers found that the 6N mice showed noticeably dampened reactions to cocaine, and that these behavioral differences could be attributed to a single locus, where a nonsynonymous mutation leads to the insertion of a phenylalanine in the resulting protein, called cytoplasmic FMRP interacting protein 2, rather than a serine.

The change appeared to destabilize the protein, which plays a role in the formation of dendritic spines on neurons. Sure enough, 6N mice had fewer spines and produced fewer electrical signals in the nucleus accumbens area, a brain region associated with drug reward.

The work not only reveals a new player in the regulation of cocaine response in mammals, but also raises questions about how similar C57BL substrains really are. “People who are not card-carrying mouse geneticists might think a Black 6 is the same no matter where it comes from,” Takahashi told ScienceNews. “People would like to think they are the same, but they’re not.”

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Avatar of: JAF


Posts: 8

January 9, 2014

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Always amazed at rediscovering the wheel.  Geneticists have know for at least 20 years (longer?) that C57/Bl6J and C57Bl/6N were different.  Recently a sequence comparison showed lots of differences (  The strains were separated in 1951 and there are lots of sublines that everyone should know are not the same.


By the way- mouse doesn't look back on the screen, Maybe a brown strain?

Avatar of: Vivekdna


Posts: 1

Replied to a comment from JAF made on January 9, 2014

January 16, 2014

JAF - the paper describes the identification of a single variant that regulates cocaine response utilizing mouse substrains.  To the best of my knowledge, this is the first demostration of a behavioral QTL being identified using substains.  

Regarding your comment that people have known for 20 years that these strains are different - these strains diverged over 60 years ago, but many users do not document the subtrain of mice that they use, simply stating they use 'C57BL/6' mice.  

This work serves as caution as well as a template to use mouse substrains as a discovery tool - certainly not "rediscovering the wheel" 

I agree the mouse picture from wikipedia does not look like C57BL/6.



Vivek Kumar


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