Adenovirus-mediated NMDA receptor knockouts in the rat hippocampal CA1 region.
Adenoviral antisense constructs of the rat N-methyl-D-aspartate (NMDA) receptor subunit 1 (R1) were assessed for creating NMDAR1 knockouts in rat hippocampal CA1 regions in vivo. In situ hybridization analyses showed that virus-derived antisense transcripts were detected up to 5 weeks postinfection (p.i.). Although immunological methods failed to demonstrate a reduction of NMDA receptor protein, whole-cell recording showed that neurons in the transduced regions were deficient in NMDA receptor-mediated synaptic currents, but not alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR)-mediated synaptic currents. Thus, the data suggest that adenovirus technology can be used to locally knockout specific gene function for dissecting molecular mechanisms of synaptic plasticity.
Kammesheidt
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Department of Psychobiology, University of California, Irvine 92697-4550, USA.
Kato
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Ito
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Sumikawa
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000256:Adenoviridae; D000595:Amino Acid Sequence; D000818:Animals; D006624:Hippocampus / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D017966:Pyramidal Cells / Q000502:physiology*; D016372:RNA, Antisense / Q000096:biosynthesis*; D051381:Rats; D011922:Rats, Mutant Strains; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D013569:Synapses / Q000502:physiology*; D014158:Transcription, Genetic
D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D010446:Peptide Fragments; D016372:RNA, Antisense; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate