Mice Deficient in the α7 Neuronal Nicotinic Acetylcholine Receptor Lack α-Bungarotoxin Binding Sites and Hippocampal Fast Nicotinic Currents

Journal of Neuroscience - Tập 17 Số 23 - Trang 9165-9171 - 1997
Avi Orr‐Urtreger1,2, Finn M. Göldner3, Mayuko Saeki3, Isabel Lorenzo1,2, Leah Goldberg1,2, Mariella De Biasi4, John A. Dani3, James W. Patrick3, Arthur L. Beaudet1,2
1Department of Molecular and Human Genetics;
2The Howard Hughes Medical Institute, Houston, Texas 77030
3Division of Neuroscience and
4Department of Molecular Physiology and Biophysics, Baylor College of Medicine, and

Tóm tắt

The α7 subunit of the neuronal nicotinic acetylcholine receptor (nAChR) is abundantly expressed in hippocampus and is implicated in modulating neurotransmitter release and in binding α-bungarotoxin (α-BGT). A null mutation for the α7 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 [3H]nicotine revealed no detectable abnormalities of high-affinity nicotine binding sites, but there was an absence of high-affinity [125I]α-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 α-BGT binding sites are equivalent to the α7-containing nAChRs that mediate fast, desensitizing nicotinic currents in the hippocampus. These mice demonstrate that the α7 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 productin vivo.

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Journal of Neuroscience

Tập 17 Số 23

9165-9171

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