C57BL/6N mutation in Cytoplasmic FMRP interacting protein 2 regulates cocaine response.
Science 2013 Dec 20; 342(6165):1508-12.
The inbred mouse C57BL/6J is the reference strain for genome sequence and for most behavioral and physiological phenotypes. However, the International Knockout Mouse Consortium uses an embryonic stem cell line derived from a related C57BL/6N substrain. We found that C57BL/6N has a lower acute and sensitized response to cocaine and methamphetamine. We mapped a single causative locus and identified a nonsynonymous mutation of serine to phenylalanine (S968F) in Cytoplasmic FMRP interacting protein 2 (Cyfip2) as the causative variant. The S968F mutation destabilizes CYFIP2, and deletion of the C57BL/6N mutant allele leads to acute and sensitized cocaine-response phenotypes. We propose that CYFIP2 is a key regulator of cocaine response in mammals and present a framework to use mouse substrains to identify previously unknown genes and alleles regulating behavior. Science 2013 Dec 20; 342(6165):1508-12.
Kumar, Vivek; Kim, Kyungin; Joseph, Chryshanthi; Kourrich, Saïd; Yoo, Seung-Hee; Huang, Hung Chung; Vitaterna, Martha H; de Villena, Fernando Pardo-Manuel; Churchill, Gary; Bonci, Antonello; and Takahashi, Joseph S, "C57BL/6N mutation in Cytoplasmic FMRP interacting protein 2 regulates cocaine response." (2013). Faculty Research 2013. 190.