The neuronal nicotinic acetylcholine receptor {alpha}7 subunit gene: Cloning, mapping, structure, and targeting in mouse

Title: The neuronal nicotinic acetylcholine receptor {alpha}7 subunit gene: Cloning, mapping, structure, and targeting in mouse

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Abstract

The neuronal nicotinic acetylcholine receptor {alpha}7 subunit is a member of a family of ligand-gated ion channels, and is the only subunit know to bind {alpha}-bungarotoxin in mammalian brain. {alpha}-Bungarotoxin binding sites are known to be more abundant in the hippocampus of mouse strains that are particularly sensitive to nicotine-induced seizures. The {alpha}7 receptor is highly permeable to calcium, which could suggest a role in synaptic plasticity in the nervous system. Auditory gating deficiency, an abnormal response to a second auditory stimulus, is characteristic of schizophrenia. Mouse strains that exhibit a similar gating deficit have reduced hippocampal expression of the {alpha}7 subunit. We have cloned and sequenced the full length cDNA for the mouse {alpha}7 gene (Acra-7) and characterized its gene structure. The murine {alpha}7 shares amino acid identity of 99% and 93% with the rat and human {alpha}7 subunits, respectively. Using an interspecies backcross panel, the murine gene was mapped to chromosome 7 near the p locus, a region syntenic with human chromosome 15; the human gene (CHRNA7) was confirmed to map to 15q13-q14 by FISH. To generate a mouse {alpha}7 mutant by homologous recombination, we have constructed a replacement vector which will delete transmembrane domains II-IV and themore »« less

Authors:

Orr-Urtreger, A; Baldini, A; Beaudet, A L ^[1]

Howard Hughes Medical Institute, Houston, TX (United States); and others

Publication Date:: 1994-09-01

OSTI Identifier:: 133857

Report Number(s):: CONF-941009-
Journal ID: AJHGAG; ISSN 0002-9297; TRN: 95:005313-0591

Resource Type:: Journal Article

Journal Name:: American Journal of Human Genetics

Additional Journal Information:: Journal Volume: 55; Journal Issue: Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994

Country of Publication:: United States

Language:: English

Subject:: 55 BIOLOGY AND MEDICINE, BASIC STUDIES; GENES; DNA-CLONING; GENETIC MAPPING; STRUCTURE-ACTIVITY RELATIONSHIPS; GENE RECOMBINATION; MICE; NERVOUS SYSTEM DISEASES; MENTAL DISORDERS; COMPARATIVE EVALUATIONS; CHIMERAS; ACETYLCHOLINE; RECEPTORS; RATS; HUMAN POPULATIONS; HUMAN CHROMOSOME 15; DNA HYBRIDIZATION; FLUORESCENCE; LIGANDS; NICOTINE; CALCIUM; DNA SEQUENCING; AMINO ACID SEQUENCE

Citation Formats


                    Orr-Urtreger, A, Baldini, A, and Beaudet, A L. The neuronal nicotinic acetylcholine receptor {alpha}7 subunit gene: Cloning, mapping, structure, and targeting in mouse.  United States: N. p., 1994. 
        Web.

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                    Orr-Urtreger, A, Baldini, A, & Beaudet, A L. The neuronal nicotinic acetylcholine receptor {alpha}7 subunit gene: Cloning, mapping, structure, and targeting in mouse.  United States.

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                    Orr-Urtreger, A, Baldini, A, and Beaudet, A L. Thu .  
        "The neuronal nicotinic acetylcholine receptor {alpha}7 subunit gene: Cloning, mapping, structure, and targeting in mouse".  United States.

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@article{osti_133857,

  title        = {The neuronal nicotinic acetylcholine receptor {alpha}7 subunit gene: Cloning, mapping, structure, and targeting in mouse},

  author       = {Orr-Urtreger, A and Baldini, A and Beaudet, A L},

  abstractNote = {The neuronal nicotinic acetylcholine receptor {alpha}7 subunit is a member of a family of ligand-gated ion channels, and is the only subunit know to bind {alpha}-bungarotoxin in mammalian brain. {alpha}-Bungarotoxin binding sites are known to be more abundant in the hippocampus of mouse strains that are particularly sensitive to nicotine-induced seizures. The {alpha}7 receptor is highly permeable to calcium, which could suggest a role in synaptic plasticity in the nervous system. Auditory gating deficiency, an abnormal response to a second auditory stimulus, is characteristic of schizophrenia. Mouse strains that exhibit a similar gating deficit have reduced hippocampal expression of the {alpha}7 subunit. We have cloned and sequenced the full length cDNA for the mouse {alpha}7 gene (Acra-7) and characterized its gene structure. The murine {alpha}7 shares amino acid identity of 99% and 93% with the rat and human {alpha}7 subunits, respectively. Using an interspecies backcross panel, the murine gene was mapped to chromosome 7 near the p locus, a region syntenic with human chromosome 15; the human gene (CHRNA7) was confirmed to map to 15q13-q14 by FISH. To generate a mouse {alpha}7 mutant by homologous recombination, we have constructed a replacement vector which will delete transmembrane domains II-IV and the cytoplasmic domain from the gene product. Recombinant embryonic stem (ES) cell clones were selected and used to develop mouse chimeras that are currently being bred to obtain germline transmission.},

  doi          = {},

  url          = {https://www.osti.gov/biblio/133857},
  journal      = {American Journal of Human Genetics},
number       = Suppl.3,

  volume       = 55,

  place        = {United States},

  year         = {1994},

  month        = {9}

}

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