Knock in transgenic mammal containing a non-functional N-terminus of Kv beta 1.1 subunit

摘要

This invention provides a transgenic mammal containing a defective beta 1 subunit (Kvbeta1) of a voltage sensitive potassium channel, where the Kvbeta1 subunit is unable to confer N-type inactivation of the K+ but retains the ability to co-associate with Kv1 family alpha-subunits and thereby enhance channel surface expression. Preferably the Kvbeta1.1 gene encoding Kvbeta1 subunit has a mutation in all or a portion of codons 1-70 of its inactivation domain. The transgenic mammal is useful as a model for psychiatric and neurological disorders to identify anxiolytic compounds and pro-cognitive functions. The invention also provides for methods for screening and evaluating test compounds for their ability to modulate Kvbeta1.1 activity, specifically for inactivation of a potassium channel or for co-association with alpha-subunits.