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  Impaired NMDA receptor function in mouse olfactory bulb neurons by tetracycline-sensitive NR1(N598R) expression

Jerecic, J., Schulze, C. H., Seeburg, P. H., Jonas, P., Sprengel, R., & Bischofsberger, J. (2001). Impaired NMDA receptor function in mouse olfactory bulb neurons by tetracycline-sensitive NR1(N598R) expression. Molecular Brain Research, 94(1), 96-104. doi:10.1016/S0169-328X(01)00221-2.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-EF56-0 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-EF57-E
Genre: Journal Article
Alternative Title : Impaired NMDA receptor function in mouse olfactory bulb neurons by tetracycline-sensitive NR1(N598R) expression

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MolBrainRes_94_2001_96.pdf (Any fulltext), 725KB
 
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 Creators:
Jerecic, Jasna1, Author              
Schulze, Christian H., Author
Seeburg, Peter H.1, Author              
Jonas, Peter2, Author              
Sprengel, Rolf1, 3, Author              
Bischofsberger, Josef, Author
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              
2Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497701              
3Rolf Sprengel Group, Max Planck Institute for Medical Research, Max Planck Society, ou_1497741              

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Free keywords: Neurotransmitters: modulators, transporters and receptors; Excitatory amino acid receptors: structure, function and expression; NMDA receptor; Mg2+ block; Ca2+ influx; Transgenic mouse; Tet-System
 Abstract: High Ca2+ permeability and its control by voltage-dependent Mg2+ block are defining features of NMDA receptors. These features are lost if the principal NR1 subunit carries an asparagine (N) to arginine (R) substitution in a critical channel site at NR1 position 598. NR1(R) expression from a single allele in gene-targeted NR1+/R mice is lethal soon after birth, precluding analysis of altered synaptic functions later in life. We therefore employed the forebrain specific small alpha, GreekCaMKII promoter to drive tTA-mediated tetracyclin sensitive transcription of transgenes for NR1(R) and for lacZ as reporter. Transgene expression was observed in cortex, striatum, hippocampus, amygdala and olfactory bulb and was mosaic in all these forebrain regions. It was highest in olfactory bulb granule cells, in most of which Ca2+ permeability and voltage-dependent Mg2+ block of NMDA receptors were reduced to different extents. This indicates significant impairment of NMDA receptor function by NR1(R) in presence of the wild-type NR1 complement. Indeed, even though NR1(R) mRNA constituted only 18% of the entire NR1 mRNA population in forebrain, the transgenic mice died during adolescence unless transgene expression was suppressed by doxycycline. Thus, glutamate receptor function can be altered in the mouse by regulated NR1(R) transgene expression.

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Language(s): eng - English
 Dates: 20012001-07-242001-10-19
 Publication Status: Published in print
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
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Title: Molecular Brain Research
  Other : Mol. Brain Res.
Source Genre: Journal
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Publ. Info: Amsterdam : Elsevier
Pages: - Volume / Issue: 94 (1) Sequence Number: - Start / End Page: 96 - 104 Identifier: ISSN: 0169-328X
CoNE: https://pure.mpg.de/cone/journals/resource/954925385137_4