C57BL/6N Mutation in Cytoplasmic FMRP interacting protein 2 Regulates Cocaine Response
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Not All Mice Are Equal: Different laboratories often use different strains of inbred animals, but one cannot make behavioral comparisons and assume that their reaction to interventions will necessarily be similar. Kumar et al. (p. 1508 ) have detected differences in cocaine response between the widely used C57BL/6N and C57BL/6J mouse strains and used quantitative trait locus analysis to identify a mutation in an inducible gene, Cyfip , that interacts with the Fragile X protein (FMRP) to regulate sensitivity and sensitization to cocaine through regulation of neuronal connectivity.
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CYFIP2 is destabilized by the Ser968Phe mutation.
“CYFIP2 is destabilized by the Ser968Phe mutation, and deletion of the allele in C57BL/6N mice results in acute and sensitized cocaine response phenotypes, suggesting that CYFIP2 is a critical regulator of the cocaine response171.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [171]
Deletion of the Cyfip2 allele in C57BL/6N mice results in acute and sensitized cocaine response phenotypes.
“CYFIP2 is destabilized by the Ser968Phe mutation, and deletion of the allele in C57BL/6N mice results in acute and sensitized cocaine response phenotypes, suggesting that CYFIP2 is a critical regulator of the cocaine response171.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [171]
C57BL/6 mouse substrains have different locomotor activities and sensitized responses to cocaine and methamphetamine.
“C57BL/6 mouse substrains have different locomotor activities and sensitized responses to cocaine and methamphetamine.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [171]
Genetic screening of C57BL/6N mice, which have a low acute and sensitized response to psychostimulants compared with C57BL/6J mice, identified a Ser968Phe mutation in Cyfip2 as a causative variant.
“Genetic screening of C57BL/6N mice, which have a low acute and sensitized response to psychostimulants compared with C57BL/6J mice, identified a Ser968Phe mutation in Cyfip2 as a causative variant171.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [171]
CYFIP2 is a critical regulator of the cocaine response.
“CYFIP2 is destabilized by the Ser968Phe mutation, and deletion of the allele in C57BL/6N mice results in acute and sensitized cocaine response phenotypes, suggesting that CYFIP2 is a critical regulator of the cocaine response171.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [171]
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- Authors
- Kumar, V., Kim, K., Joseph, C., Kourrich, S., Yoo, S.-H., Huang, H. C., Vitaterna, M. H., Pardo-Manuel de Villena, F., Churchill, G., Bonci, A., & Takahashi, J. S.
- Affiliations
- Howard Hughes Medical Institute (US)
- The University of Texas Southwestern Medical Center (US)
- Intramural Research Program, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Baltimore, MD 21224, USA.
- Northwestern University (US)
- Department of Genetics, University of North Carolina–Chapel Hill, Chapel Hill, NC 27599, USA.
- Jackson Laboratory (US)
- National Institutes of Health (US)
- Corresponding author
- Takahashi, Joseph S.
- ORCID
- Venue
- Science
- Published
- 2013-12-20
- Volume
- 342
- Issue
- 6165
- Pages
- 1508-1512
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4500108
- OpenAlex
- W2001644882
- Cited by
- 187
- References
- 6
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 9 · 2023: 10 · 2022: 18 · 2021: 16 · 2020: 20 · 2019: 20 · 2018: 19 · 2017: 15 · 2016: 11 · 2015: 14 · 2014: 17 · 2012: 1
- FWCI
- 5.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- UNC Libraries
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute of Mental Health (U01MH061915)
- National Institute on Drug Abuse (F32DA024556)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- CYFIP2, cocaine sensitization, protein destabilization, behavioral genetics, inbred mouse strains
- MeSH terms
- Central Nervous System Stimulants, Animals, Cocaine, Methamphetamine, Mice, Inbred C57BL, Motor Activity, Mutation, Nerve Tissue Proteins, Phenylalanine, Psychomotor Performance, Serine, Mice, Knockout, Amino Acid Substitution, Cocaine-Related Disorders, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Adaptor Proteins, Signal Transducing, Mice, Drug-Seeking Behavior
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