C57BL/6N mutation in cytoplasmic FMRP interacting protein 2 regulates cocaine response

Vivek Kumar, Kyungin Kim, Chryshanthi Joseph, Saïd Kourrich, Seung Hee Yoo, Hung Chung Huang, Martha H. Vitaterna, Fernando Pardo Manuel De Villena, Gary Churchill, Antonello Bonci, Joseph S. Takahashi

Research output: Contribution to journalArticle

78 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1508-1512
Number of pages5
JournalScience
Volume342
Issue number6165
DOIs
StatePublished - 2013

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Cocaine
Mouse
Protein
Mutation
Phenotype
Allele
Causative
Gene
Mammals
Genome
Stem Cells
Locus

ASJC Scopus subject areas

  • History and Philosophy of Science
  • General

Cite this

C57BL/6N mutation in cytoplasmic FMRP interacting protein 2 regulates cocaine response. / 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; Takahashi, Joseph S.

In: Science, Vol. 342, No. 6165, 2013, p. 1508-1512.

Research output: Contribution to journalArticle

Kumar, V, Kim, K, Joseph, C, Kourrich, S, Yoo, SH, Huang, HC, Vitaterna, MH, De Villena, FPM, Churchill, G, Bonci, A & Takahashi, JS 2013, 'C57BL/6N mutation in cytoplasmic FMRP interacting protein 2 regulates cocaine response', Science, vol. 342, no. 6165, pp. 1508-1512. https://doi.org/10.1126/science.1245503
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 ; Takahashi, Joseph S. / C57BL/6N mutation in cytoplasmic FMRP interacting protein 2 regulates cocaine response. In: Science. 2013 ; Vol. 342, No. 6165. pp. 1508-1512.
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AU - Huang, Hung Chung

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