Generation and characterization of homozygous plasminogen-Tochigi mutant mice bearing reduced fibrinolytic activity

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860801
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Osaka University (2014); National Cardiovascular Center Research Institute (2013)
• Principal Investigator: TASHIMA Yuko 大阪大学, 微生物病研究所, 助教 (10423104)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: プラスミノーゲン / 線溶 / 静脈血栓症 / 肺塞栓 / プラスミノーゲン栃木変異

Outline of Final Research Achievements

Plasminogen (Plg) is a precursor of a serine protease, plasmin to degrade fibrin fiber in blood clot. Plg-A620T mutation previously named as Plg-Tochigi was identified in Japanese patients with deep venous thrombosis. We investigated whether the homozygous Plg-A622T mutation corresponding to human Plg-Tochigi caused serious thrombosis in mice. Compared to wild-type mice, Plg-A620T mice showed the lower activity of plasmin, but did not affect wound healing unlike Plg-KO mice. Plg-Tochigi mutation did not significantly affect the severity of thrombogenesis under three different experimental thrombosis models: a middle cerebral artery occlusion model of ischemia-reperfusion injury, acute pulmonary embolism model by injection of recombinant human tissue factor via inferior vena cava, and inferior vena cava thrombosis model with electrolytic stimulation. In conclusion, homozygous Plg-Tochigi mutation showed reduced enzymatic activity of plasmin but did not cause severe thrombosis in mice.

Free Research Field

生化学