UT Southwestern neuroscience researchers have identified a gene that controls the response to cocaine by comparing closely related strains of mice often used to study addiction and behavior patterns.
The researchers suspect that the newly identified gene, Cyfip2, determines how mammals respond to cocaine, although it is too soon to tell what the indications are for humans or for addiction, said Dr. Joseph Takahashi, chair of neuroscience and a Howard Hughes Medical Institute investigator at UT Southwestern and the senior author of the study.
The findings, reported in Science, evolved from examining the genetic differences between two substrains of the standard C57BL/6 mouse strain: a "J" strain from the Jackson Laboratory (C57BL/6J) and an "N" strain from the National Institutes of Health (C57BL/6N). Researchers compared the two strains of mice and used their differential responses to cocaine to identify the causative gene.
"We found that the 'N' strain has accumulated mutations over time, one of which has a very strong effect on cocaine response," Dr. Takahashi said. "We propose that CYFIP2 - the protein produced by the Cyfip2 gene - is a key regulator of cocaine response in mammals."
The Takahashi laboratory has identified about 100 genetic differences that affect protein sequences between the two mouse strains, meaning that there are many genetic differences whose effects are not yet known, he added.
"We identified this gene by first using a forward genetics strategy to search for differences in traits between the two mouse strains. We found a difference in cocaine response between them, with the C57BL/6N strain showing a reduced behavioral response," Dr. Takahashi said. "We then carried out genetic mapping and whole genome sequencing, which allowed us to pinpoint the Cyfip2 gene as the causative one in a rapid and unambiguous way."