Researchers have found a single nucleotide polymorphism (SNP) difference in cocaine and methamphetamine response between two different substrains of lab mice. This new insight has provided information about the gene Cyfip2 and its involvement as a regulator of cocaine response with a possible role in addiction.
Joseph Takahashi, Ph.D., of the University of Texas Southwestern Medical Center and the Howard Hughes Medical Institute, and colleagues, compared C57BL/6J mice from The Jackson Laboratory and C57BL/6N mice from colonies raised at the National Institutes of Health in terms of their sensitivities to cocaine and methamphetamine. They found that 6N mice have a lower response than the 6J mice.
Researchers were able to map the difference between these substrains of mice to a single quantitative trail locus (QTL) on chromosome 11 followed by whole-genome sequencing. They identified a SNP in a gene known as Cyfip2. This gene codes for a highly conserved protein linked to fragile X-mental retardation protein (FMRP). This complex is known as the most common cause of mental retardation in humans.
This experimental design demonstrates that variations among some 20 C57BL/6 substrains can be used as a gene-finding resource. Moreover, these variations highlight the issue of genetic quality control in mouse populations.
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The C57BL/6 mouse is the most widely used lab mouse and was developed by Jackson Laboratory founded by Clarence Cook in 1921. This was the first mouse strain to have its genome characterized.
It’s been almost century since the 6J mouse was bred so genetic drift has occurred. In other words, the genomes of substrains have diverged. Gary Churchill, Ph.D., professor at Jackson Laboratory, notes, “This means that researchers should be very cautious when comparing behavioral data from studies using 6J and 6N strains. They are clearly not interchangeable.”
To keep an eye on genetic drift, the Jackson Lab uses genetic quality control programs for its most widely used inbred strains, including C57B/6J. So, every five generations, the Jackson lab refreshes its production colonies by raising mice from cryopreserved 6J embryos. This is to prevent spontaneous mutations from altering the 6J line.