| Budget Amount *help |
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2016: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
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| Outline of Final Research Achievements |
In this study, apolipoprotein E (Apoe) gene was knocked out in spontaneously hypertensive rat (SHR) to establish a hereditary model of combined hypertension and atherosclerosis in rats. In addition to Apoe, the peroxiredoxin 2 (Prdx2) and Akt1 were knocked out to explore effects of oxidative stress and NO on atherogenesis. Gene depletion was done using the CRISPR/Cas9 technology. The two knockout rats were then mated to obtain the double knockout SHRApoE(-/-)Prdx2(-/-). We successfully established 6 knockouts (2 for each of the three genes), and one double knockout. According to phenotype analyses, there was no significant difference in blood pressure between SHR and SHRApoe(-/-). The total cholesterol level in SHRApoe(-/-) was significantly higher than in SHR under a high-fat diet. Clear fat deposition in the aorta was observed in SHRApoe(-/-) and SHRApoe(-/-)Prd2x(-/-). These rats would be useful models for CVDs.
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