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

Journal Article · Thu Sep 01 00:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:133857

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

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

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.

• OSTI ID: 133857
• Report Number(s): CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0591
• Journal Information: American Journal of Human Genetics, Vol. 55, 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

Related Subjects

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