Cited by 225Nicotinic Acetylcholine Receptors StudyNeuroscience and Neuropharmacology ResearchSmoking Behavior and Cessation

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Neuronal nicotinic acetylcholine receptor subunit knockout mice: physiological and behavioral phenotypes and possible clinical implications

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Picciotto, Marina R, Caldarone, Barbara J, Brunzell, Darlene H, Zachariou, Venetia, Stevens, Tanya R, King, Sarah L·2001·Pharmacology & Therapeutics

DOI 10.1016/s0163-7258(01)00161-9

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Abstract

Nicotinic acetylcholine receptors (nAChRs) in the muscle, autonomic ganglia, and brain are targets for pharmacologically administered nicotine. Several of the subunits that combine to form neuronal nicotinic receptors have been deleted by knockout or mutated by knockin in mice using homologous recombination. We will review the biochemical, pharmacological, anatomical, physiological, and behavioral phenotypes of mice with genetically altered neuronal nAChR subunits. Clinically relevant mutations in nAChR genes will also be discussed. In addition, some of the signal transduction pathways activated through nAChRs will be described in order to delineate the longer-term changes that might result from persistent activation or inactivation of nAChRs. Genetically manipulated mice have greatly increased our understanding of the subunit composition and physiological properties of nAChRs in vivo. In addition, these mice have provided a model system to determine the molecular basis for many of the pharmacological actions of nicotine on neurotransmitter release and behavior. Genetic manipulations in mice have also elucidated the role of nAChR subunits in various disease states, and suggest several avenues for drug development.

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Authors: Picciotto, M. R., Caldarone, B. J., Brunzell, D. H., Zachariou, V., Stevens, T. R., & King, S. L.
Affiliations: Yale University (US)
Corresponding author: Picciotto, Marina R
ORCID: Picciotto, Marina R
Caldarone, Barbara J
Zachariou, Venetia
King, Sarah L
Venue: Pharmacology & Therapeutics
Publisher: Elsevier BV
Published: 2001-11
Volume: 92
Issue: 2-3
Pages: 89-108
ISSN: 0163-7258 (ISSN-L)
DOI: 10.1016/s0163-7258(01)00161-9
OpenAlex: W2053266420
Cited by: 221
References: 176
Citations by year: 2026: 2 · 2025: 3 · 2024: 11 · 2023: 5 · 2022: 3 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 6 · 2015: 10 · 2014: 14 · 2013: 2 · 2012: 17
FWCI: 0.62
Type: journal article
Language: en
Open access: green
figshare.com
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Pharmacology & Therapeutics (publishedVersion)
PubMed (publishedVersion)
Figshare (submittedVersion, cc-by)
Sussex Research Online (University of Sussex) (submittedVersion)
Funders: National Institutes of Health
National Institute on Drug Abuse (DA 10455, DA84733, DA 00436)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
Keywords: neuronal nicotinic acetylcholine receptors, nicotine pharmacology, signal transduction, neurotransmitter release, behavioral phenotypes, physiological phenotypes, drug development
MeSH terms: Animals, Anxiety, Electrophysiology, Learning, Memory, Neurons, Nicotine, Phenotype, Receptors, Nicotinic, Signal Transduction, Point Mutation, Mice, Knockout, Nicotinic Agonists, Mice

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Neuronal nicotinic acetylcholine receptor subunit knockout mice: physiological and behavioral phenotypes and possible clinical implications

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