VARIANT NEURONAL NICOTINIC ALPHA-7 RECEPTOR AND METHODS OF USE

摘要

The present invention relates to a variant of the nicotinic acetylcholine receptor (nAChR) alpha7 subunit having a substitution within its second transmembrane (TM2) domain. Specifically, the sixth amino acid position within the TM2 domain has the point mutation T-> S, such that threonine-244 becomes serine-244. Advantageously, the alpha7 variant of the present invention retains the essential drug sensitivities of the wild-type alpha7 receptor, but does not exhibit the response-limiting form of fast desensitization. Therefore, the alpha7 variant is a "gain of function" mutant that is particularly useful for testing new pharmacological agents. The present invention includes the T6'S variant TM2 domain, T6'S variant alpha7 subunit, and T6'S variant nACh receptor polypeptides, polynucleotides encoding these polypeptides, recombinant hosts expressing these polynucleotides, and assays utilizing the T6'S variant TM2 domain, T6'S variant alpha7 subunit, and/or T6'S variant nACh receptor.