Transgenic Engineering Of Cholinesterases, And Tools For Exploring Cholinergic Responses

Life Sciences & Biotechnology Update, Feb, 2001

This translation from Israel (Hebrew University) addresses a program involving cholinesterases and cholinergic responses. During the year 1998, progress was made in delineating the non-catalytic roles of acetylcholinesterase, involving the construction of several expression vectors and directing their expression in transiently transgenic tadpoles of Xenopus laevis, as well as in cultured Xenopus motoneurons and rat phaeochromocytoma cells. The work further advances the creation and characterization of transgenic mice, which express several engineered variants of human acetylcholinesterase.

An intriguing feedback response was discovered, which leads to the accumulation of soluble monomeric acetylcholinesterase following acute psychological stress events, or under exposure to anti-cholinesterases. Current efforts are focussed on the development of an antisense approach, to prevent the accumulation of excess acetylcholin-esterase and thus avoid both the imbalanced cholinergic neurotransmission that is caused by such accumulation and the adverse consequences associated with the non-catalytic activities of the excess protein.

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