Transgenic Non-Human Animal Models of Ischemia-Reperfusion Injury and Uses Thereof

摘要

The present invention relates to a nucleic acid molecule encoding a K94A/K447A mutant of wild type p90 ribosomal S6 kinase (p90RSK) and DNA constructs, expression vectors, and hosts including the mutant p90RSK-encoding molecule. The present invention also relates to two transgenic non-human animal models of ischemic reperfusion (I/R) damage, the first animal having a transgene encoding a mutant p90RSK that is rendered kinase inactive for S703 phosphorylation of NHE1 and the second animal having a transgene encoding for cardiac-specific overexpression of wild type p90RSK in the animal that provides a model for diabetic cardiomyopathy. Also provided are methods for generating transgenic non-human animal models of ischemic reperfusion (I/R) damage; for using the transgenic cells for identifying an agent capable of inhibiting p90RSK-induced I/R damage; for identifying agents that modulate I/R injury resulting from an ischemic event; and for treating individuals to inhibit I/R injury following an ischemic event.