RbAp48 transgenic mice for drug discovery in age-related memory decline

摘要

Described is a transgenic mouse with two transgenes, each of which transgene comprises a DNA sequence encoding a dominant negative form of RbAp48 protein, wherein the expression of the dominant negative form of RbAp48 is spatially restricted to the forebrain by a CaM Kinase IIa promoter and wherein the expression of the dominant negative form of RbAp48 is controlled by tetracycline-controlled transcriptional activation. Also provided are methods for evaluating in the transgenic mouse the potential therapeutic effect of an agent for slowing, inhibiting or preventing age-related memory decline in a mammalian subject.

主权项

1. A transgenic mouse whose genome comprises:
i) a nucleic acid sequence encoding a dominant negative RbAp48 (RbAp48-DN) protein operably linked to a tetracycline promoter; and ii) a nucleic acid sequence encoding a tetracycline controlled transactivator (tTA) operably linked to a CaM Kinase IIa promoter, wherein expression of the RbAp48-DN is restricted to the forebrain, and wherein said mouse is capable of having a memory deficit as compared to a wild-type mouse upon administration of tetracycline.