ANIMAL MODEL OF CHOLINERGIC DYSFUNCTION TO EVALUATE COGNITIVE ENHANCERS AND DRUGS THAT IMPROVE MYASTHENIA

摘要

Recombinant non-human mammals having reduced or no expression of vesicular acetylcholine transporter protein (VAChT) as compared to the corresponding wild-type mammal are provided. The mammal may have, e.g., impaired performance in object and social recognition and/or impaired neuromuscular performance and/or alterations in autonomic nervous system function as compared to the corresponding wild-type mammal. Methods of screening a compound for cholinergic activity or activity in treating a cholinergic neurotransmission disorder are also provided. In addition, a cell such as a nerve cell isolated from a mammal as described herein is provided, along with cell cultures, which are useful in vitro for screening the activity of candidate compounds for their effect on cholinergic neurotransmission, and for their activity in treating cholinergic neurotransmission disorders.