Neuronal nicotinic acetylcholine receptor subunit knockout mice: physiological and behavioral phenotypes and possible clinical implications
Open accessAbstract
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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Nicotinic receptors function as non-selective, excitatory cation channels.
“Nicotinic receptors function as non-selective, excitatory cation channels (Changeux et al., 1998; Picciotto et al., 2001) and occur as homomeric or heteromeric assemblies of a large family of α- and β-subunits (α2-α7 and β2-β4; reviewed in (Picciotto et al., 2000)).”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Picciotto et al., 2001
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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
- Venue
- Pharmacology & Therapeutics
- Publisher
- Elsevier BV
- Published
- 2001-11
- Volume
- 92
- Issue
- 2-3
- Pages
- 89-108
- ISSN
- 0163-7258 (ISSN-L)
- 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
- 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 › Physiology › 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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