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TRANSGENIC NON-HUMAN ANIMAL MODELS OF ISCHEMIA-REPERFUSION INJURY AND USES THEREOF
TRANSGENIC NON-HUMAN ANIMAL MODELS OF ISCHEMIA-REPERFUSION INJURY AND USES THEREOF
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机译:缺血再灌注损伤的转基因非人类动物模型及其应用
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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.
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