Cited by 177Nicotinic Acetylcholine Receptors StudyParkinson's Disease Mechanisms and TreatmentsNeuroscience and Neuropharmacology Research

Point mutant mice with hypersensitive α4 nicotinic receptors show dopaminergic deficits and increased anxiety

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Labarca, Cesar, Schwarz, Johannes, Deshpande, Purnima, Schwarz, Sigrid, Nowak, Mark W., Fonck, Carlos, Nashmi, Raad, Kofuji, Paulo +9 more·2001·Proceedings of the National Academy of Sciences

Abstract

Knock-in mice were generated that harbored a leucine-to-serine mutation in the α4 nicotinic receptor near the gate in the channel pore. Mice with intact expression of this hypersensitive receptor display dominant neonatal lethality. These mice have a severe deficit of dopaminergic neurons in the substantia nigra, possibly because the hypersensitive receptors are continuously activated by normal extracellular choline concentrations. A strain that retains the neo selection cassette in an intron has reduced expression of the hypersensitive receptor and is viable and fertile. The viable mice display increased anxiety, poor motor learning, excessive ambulation that is eliminated by very low levels of nicotine, and a reduction of nigrostriatal dopaminergic function upon aging. These knock-in mice provide useful insights into the pathophysiology of sustained nicotinic receptor activation and may provide a model for Parkinson's disease.

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  1. [4]4. Wonnacott, S., Russell, M. A. H. & Stolerman, I. P. (Oxford Univ. Press, Oxford), pp. 226-277.
  2. [5]5. Picciotto, M. R., Zoli, M., Zachariou, V. & Changeux, J.-P. (1997) Biochem. Soc. Trans. 25, 824-829.
  3. [25]25. Zhong, W., Gallivan, J., Zhang, Y., Li, L., Lester, H. & Dougherty, D. (1998) Proc. Natl. Acad. Sci. USA 95, 12088-12093.
  4. [33]33. Zhou, M., Engel, A. G. & Auerbach, A. (1999) Proc. Natl. Acad. Sci. USA 96, 10466-10471.

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Authors
Labarca, C., Schwarz, J., Deshpande, P., Schwarz, S., Nowak, M. W., Fonck, C., Nashmi, R., Kofuji, P., Dang, H., Shi, W., Fidan, M., Khakh, B. S., Chen, Z., Bowers, B. J., Boulter, J., Wehner, J. M., & Lester, H. A.
Affiliations
California Institute of Technology (US)
Corresponding author
  • Schwarz, Johannes
  • Deshpande, Purnima
  • Lester, Henry A.
Venue
Proceedings of the National Academy of Sciences
Published
2001-02-20
Volume
98
Issue
5
Pages
2786-2791
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2073702980
Cited by
177
References
38
Citations by year
2023: 4 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 6 · 2017: 6 · 2016: 7 · 2015: 12 · 2014: 6 · 2013: 2 · 2012: 7
FWCI
5.35
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
Funders
  • Alexander von Humboldt-Stiftung
  • Tobacco-Related Disease Research Program
  • Wellcome Trust
  • National Institutes of Health (5t01mh019176-03, -10156, NS-1 1756, 5p01da010156-05, 5r03da011836-02)
  • National Institute of Mental Health (MH-19176)
  • National Institute on Drug Abuse (DA-11836, P50DA005010, DA10156)
  • National Institute of Neurological Disorders and Stroke (NS 11756, R01NS011756)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
knock-in mice, neonatal lethality, dopaminergic neurons, substantia nigra, choline, anxiety, motor learning, ambulation, nicotine, nigrostriatal pathway, Parkinson's disease model, aging
MeSH terms
Animals, Anxiety, Dopamine, Female, Heterozygote, Immunohistochemistry, Mice, Mutant Strains, Pregnancy, Receptors, Nicotinic, Point Mutation, Mice, Rats

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