Establishment of a genetic rat model for combined hypertension and atherosclerosis using the genome editing technology.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293086
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Shimane University
• Principal Investigator: NABIKA TORU 島根大学, 医学部, 教授 (50180534)
• Co-Investigator(Kenkyū-buntansha): 家森 幸男 武庫川女子大学, 付置研究所, 教授 (80025600) ; 真下 知士 大阪大学, 医学(系)研究科(研究院), 准教授 (80397554)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 疾患モデル動物 / 高血圧 / 動脈硬化 / ゲノム編集 / ノックアウト

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.

Free Research Field

基礎医学、実験病理学、実験動物学