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 mod ulating neurotransmitter release and in binding alpha-bungarotoxin (al pha-BGT). A null mutation for the alpha 7 subunit was prepared by dele ting the last three exons of the gene. Mice homozygous for the null mu tation lack detectable mRNA, but the mice are viable and anatomically normal. Neuropathological examination of the brain revealed normal str ucture and cell layering, including normal cortical barrel fields; his tochemical assessment of the hippocampus was also normal. Autoradiogra phy with [H-3]nicotine revealed no detectable abnormalities of high-af finity nicotine binding sites, but there was an absence of high-affini ty [I-125]alpha-BGT sites. Null mice also lack rapidly desensitizing, methyllycaconitine-sensitive, nicotinic currents that are present in h ippocampal 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. Th ese mice demonstrate that the alpha 7 subunit is not essential for nor mal development or for apparently normal neurological function, but th e mice may prove to have subtle phenotypic abnormalities and will be v aluable in defining the functional role of this gene product in vivo.