Point mutant mice with hypersensitive α4 nicotinic receptors show dopaminergic deficits and increased anxiety
| Autor: | Jeanne M. Wehner, Barbara J. Bowers, Paulo Kofuji, Mark W. Nowak, Jim Boulter, Purnima Deshpande, Johannes Schwarz, Cesar Labarca, Wenmei Shi, Melihat Fidan, Sigrid Schwarz, Zhou-Feng Chen, Raad Nashmi, Hong Dang, Carlos Fonck, Henry A. Lester, Baljit S. Khakh |
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| Rok vydání: | 2001 |
| Předmět: |
Heterozygote
medicine.medical_specialty Dopamine Substantia nigra Anxiety Receptors Nicotinic Biology Nicotine Mice chemistry.chemical_compound Pregnancy Internal medicine Extracellular medicine Animals Point Mutation Choline Receptor Multidisciplinary Dopaminergic Biological Sciences Immunohistochemistry Mice Mutant Strains Rats Nicotinic agonist Endocrinology chemistry Female medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 98:2786-2791 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.041582598 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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