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Volume 17, Number 23, Issue of December 1, 1997 pp. 9165-9171

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

Received July 31, 1997; revised Sept. 16, 1997; accepted Sept. 18, 1997.

Avi Orr-Urtreger^{1, 4}, Finn M. Göldner², Mayuko Saeki², Isabel Lorenzo^{1, 4}, Leah Goldberg^{1, 4}, Mariella De Biasi³, John A. Dani², James W. Patrick², and Arthur L. Beaudet^{1, 4}

¹ Department of Molecular and Human Genetics, ² Division of Neuroscience, and ³ Department of Molecular Physiology and Biophysics, Baylor College of Medicine, and ⁴ The Howard Hughes Medical Institute, Houston, Texas 77030

The 7 subunit of the neuronal nicotinic acetylcholine receptor (nAChR) is abundantly expressed in hippocampus and is implicated in modulating neurotransmitter release and in binding -bungarotoxin (-BGT). A null mutation for the 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 [³H]nicotine revealed no detectable abnormalities of high-affinity nicotine binding sites, but there was an absence of high-affinity [¹²⁵I]-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 -BGT binding sites are equivalent to the 7-containing nAChRs that mediate fast, desensitizing nicotinic currents in the hippocampus. These mice demonstrate that the 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.

Key words: acetylcholine receptor; -bungarotoxin; gene targeting; hippocampus; mouse; nicotine; 7 subunit

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