C57BL/6N mutation in Cytoplasmic FMRP interacting protein 2 regulates cocaine response.
Document Type
Article
Publication Date
12-20-2013
JAX Source
Science 2013 Dec 20; 342(6165):1508-12.
Volume
342
Issue
6165
First Page
1508
Last Page
1512
ISSN
1095-9203
PMID
24357318
Abstract
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.
Recommended Citation
Kumar V,
Kim K,
Joseph C,
Kourrich S,
Yoo S,
Huang H,
Vitaterna M,
de Villena F,
Churchill G,
Bonci A,
Takahashi J.
C57BL/6N mutation in Cytoplasmic FMRP interacting protein 2 regulates cocaine response. Science 2013 Dec 20; 342(6165):1508-12.