TY - JOUR
T1 - C57BL/6N mutation in cytoplasmic FMRP interacting protein 2 regulates cocaine response
AU - Kumar, Vivek
AU - Kim, Kyungin
AU - Joseph, Chryshanthi
AU - Kourrich, Saïd
AU - Yoo, Seung Hee
AU - Huang, Hung Chung
AU - Vitaterna, Martha H.
AU - De Villena, Fernando Pardo Manuel
AU - Churchill, Gary
AU - Bonci, Antonello
AU - Takahashi, Joseph S.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1245503
DO - 10.1126/science.1245503
M3 - Article
C2 - 24357318
AN - SCOPUS:84890842320
SN - 0036-8075
VL - 342
SP - 1508
EP - 1512
JO - Science
JF - Science
IS - 6165
ER -