Mice Deficient in the alpha 7 Neuronal Nicotinic Acetylcholine Receptor Lack alpha -Bungarotoxin Binding Sites and Hippocampal Fast Nicotinic Currents

The alpha 7 subunit of the neuronal nicotinic acetylcholine receptor (nAChR) is abundantly expressed in hippocampus and is implicated in modulating neurotransmitter release and in binding alpha -bungarotoxin ( alpha -BGT). A null mutation for the alpha 7 subunit was prepared by deleting the last thr...

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Bibliographic Details
Published in:The Journal of neuroscience 1997-12, Vol.17 (23), p.9165-9171
Main Authors: Orr-Urtreger, Avi, Goldner, Finn M, Saeki, Mayuko, Lorenzo, Isabel, Goldberg, Leah, De Biasi, Mariella, Dani, John A, Patrick, James W, Beaudet, Arthur L
Format: Article
Language:English
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Summary:The alpha 7 subunit of the neuronal nicotinic acetylcholine receptor (nAChR) is abundantly expressed in hippocampus and is implicated in modulating neurotransmitter release and in binding alpha -bungarotoxin ( alpha -BGT). A null mutation for the alpha 7 subunit was prepared by deleting the last three exons of the gene. Mice homozygous for the null mutation lack detectable mRNA, but the mice are viable and anatomically normal. Neuropathological examination of the brain revealed normal structure and cell layering, including normal cortical barrel fields; histochemical assessment of the hippocampus was also normal. Autoradiography with [ super(3)H]nicotine revealed no detectable abnormalities of high-affinity nicotine binding sites, but there was an absence of high-affinity [ super(125)I] alpha -BGT sites. Null mice also lack rapidly desensitizing, methyllycaconitine-sensitive, nicotinic currents that are present in hippocampal neurons. The results of this study indicate that the alpha -BGT binding sites are equivalent to the alpha 7-containing nAChRs that mediate fast, desensitizing nicotinic currents in the hippocampus. These mice demonstrate that the alpha 7 subunit is not essential for normal development or for apparently normal neurological function, but the mice may prove to have subtle phenotypic abnormalities and will be valuable in defining the functional role of this gene product in vivo.
ISSN:0270-6474
1529-2401