Details

Autor(en) / Beteiligte

• Labarca, Cesar
• Schwarz, Johannes
• Deshpande, Purnima
• Schwarz, Sigrid
• Nowak, Mark W.
• Fonck, Carlos
• Nashmi, Raad
• Kofuji, Paulo
• Dang, Hong
• Shi, Wenmei
• Fidan, Melihat
• Khakh, Baljit S.
• Chen, Zhoufeng
• Bowers, Barbara J.
• Boulter, Jim
• Wehner, Jeanne M.
• Lester, Henry A.

Titel

Point Mutant Mice with Hypersensitive α4 Nicotinic Receptors Show Dopaminergic Deficits and Increased Anxiety

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2001-02, Vol.98 (5), p.2786-2791

Ort / Verlag

National Academy of Sciences

Erscheinungsjahr

2001

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.