A comparative study on phenotypic and molecular characteristics of ischemic stroke resistant animal model

Abstract

The use of animal stroke models has substantially increased to develop the therapeutic agents in preclinical studies according to the high mortality rate of cardiovascular disease. Animal ischemic stroke model is generally classified into three types, global ischemia, focal ischemia, and hypoxic ischemia. These animal models have been extensively used in ischemic stroke studies. However, ischemia induced injury models reveal several limitations to identify underlying pathogenesis of stroke. The purpose of this study was to develop the stroke resistant model using ischemia induced cell death signal targeted gene, DAPK1/Pin1 deletion. In addition, stroke resistant model was screened the major phenotypes, physiological functions, and molecular characteristics in organ system. DAPK1/Pin1 single gene knockout (KO) and double gene KO (DKO) mice were generated to determine whether DAPK1 and Pin1 contribute to neuronal death in ischemic injury. The genotype was confirmed by PCR using genomic DNA. DAPK1/Pin1 DKO mice were produced by crossing female DAPK1/Pin1 heterozygous (hetero) with identical genotype male mice. The offspring from DAPK1/Pin1 hetero mice showed significant difference compared with wild type (WT). Body weight and body length of Pin1 KO and DAPK1/Pin1 DKO mice were less than WT and DAPK1 KO mice. DAPK1/Pin1 DKO mice exhibited restricted growth rate. To examine the therapeutic effects of DAPK1/Pin1 deficiency, KO mice were subjected to MCAo. DAPK1/Pin1 DKO mice exhibited smaller infarct size and reduced neurologic deficits compared with single gene KO. Taken together, ischemic stroke resistant model induced by DAPK1/Pin1 genetic suppression could be potential targets for treating stroke.Support or Funding InformationFunds: NRF‐2013R1A2A2A01067169, NRF‐2017R1A2A2A01067169, KRIBB‐KGM4611714This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.