Daniel Caballero-Rivera;Nilza M Biaggi-Labiosa;Jose A Lasalde-Dominicci;Emir Aviles-Pagan
发明人:
Jose A Lasalde-Dominicci,Nilza M Biaggi-Labiosa,Emir Aviles-Pagan,Daniel Caballero-Rivera
申请号：
US15141689
公开号：
US10676518B1
申请日:
2016.04.28
申请国别(地区):
US
年份:
2020
代理人:
摘要：
The α4β2 neuronal nicotinic acetylcholine receptor (nAChR) plays a crucial role in nicotine addiction. The invention studied the effect of subunit phosphorylation on α4β2 nAChR function and expression, and eleven residues located in the M3-M4 cytoplasmic loop were mutated to alanine and aspartic acid. When nicotine was used as an agonist, four mutations exhibited a statistically significant hypersensitivity to nicotine (S438D, S469A, Y576A, and S589A). Additionally, two mutations (S516D and T536A) that displayed normal activation with ACh displayed remarkable reductions in sensitivity to nicotine. The invention provides a knock-in mutant construct for the development of a transgenic mouse line with reduced nicotine sensitivity to be used in future studies.
