A new mouse model for pregnancy-induced hypertension.

一种新的妊娠高血压小鼠模型。

• 批准号: 09558084
• 负责人: FUKAMIZU Akiyoshi
• 金额: $ 8.26万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09558084/
• 关键词: angiotensin; pregnancy; renin; blood pressure; hypertension; transgenic mice; knock-out mice; hypertrophy

Pregnancy-induced hypertension (PIH), the commonest and most serious complications of pregnancy, usually becomes apparent in late pregnancy, the pathophysiology of which has remained elusive (1). Here, we show that later in pregnancy blood pressure is dramatically elevated in transgenic female mice expressing human angiotensinogen only when mated with male mice carrying the human renin gene, which is due to the secretion of feto-placental human renin into the maternal circulation. The observed transient elevation of blood pressure was sharply returned to the non-pregnant state after delivery. Histopathologic examinations revealed uniform enlargement of glomeruli associated with increase in urinary protein excretion, myocardial hypertrophy and necrosis and edema in placenta. These results clearly demonstrate that PIH that caused maternal morbidity and mortality is triggered by the combinatorial action of feto-placental renin genetically derived from male mice with maternal angiotensinogen in transgenic mice.

妊娠高血压综合征（PIH）是妊娠期最常见和最严重的并发症，通常在妊娠后期变得明显，其病理生理学仍然难以捉摸（1）。在这里，我们表明，在怀孕后期，表达人血管紧张素原的转基因雌性小鼠只有在与携带人血浆蛋白酶基因的雄性小鼠交配时，血压才会显着升高，这是由于胎儿胎盘人血浆蛋白酶分泌到母体循环中。观察到的血压一过性升高在分娩后急剧恢复到非妊娠状态。组织学检查显示肾小球均匀增大，伴尿蛋白排泄增加，心肌肥厚坏死，胎盘水肿。这些结果清楚地表明，妊娠高血压综合征，引起孕产妇的发病率和死亡率是触发的组合作用的胎儿胎盘肾素遗传来源于雄性小鼠与母体血管紧张素原转基因小鼠。

项目成果

Fukamizu A.: "Angiotensin II plays a pathogenic rore in immune-medicated renal injury in mine"J.Clin.Invest.. 103. 627-635 (1999)

Fukamizu A.：“血管紧张素 II 在我的免疫药物性肾损伤中发挥致病作用”J.Clin.Invest.. 103. 627-635 (1999)

Yanai,K: "Molecular variation of human angiotensinogen core promoter element located between TATA box and transcription initiation site affects its transcriptional activity." J.Biol.Chem.272. 30558-30562 (1997)

Yanai,K：“位于 TATA 盒和转录起始位点之间的人血管紧张素原核心启动子元件的分子变异会影响其转录活性。”

Fukamizu A.: "Reduction of depressive-like behavior in mice lacking angiotensinogen"Neurosci.Lett.. 261. 167-170 (1999)

Fukamizu A.：“减少缺乏血管紧张素原的小鼠的抑郁样行为”Neurosci.Lett.. 261. 167-170 (1999)

Tanimoto, Y., Tanimoto, K., Sugiyama, F., Horiguchi, H., Murakami, K., Yagami, K., and Fukamizu, A.: "Male Sterillity in Transgenic Mice Expressing Activin βA Subunit Gene in Testis"Biochem. Biophys. Res. Commun.. 259. 699-705 (1999)

Tanimoto, Y.、Tanimoto, K.、Sugiyama, F.、Horiguchi, H.、Murakami, K.、Yagami, K. 和 Fukamizu, A.：“睾丸中表达激活素 βA 亚基基因的转基因小鼠的雄性不育”生物化学研究。259。699-705（1999）

Kihara,M.: "The neuronal isoform of constitutive nitric oxide synthase is upregulated in the macula densa of angiotensinogen gene-knockout mice." Lab.Invest.76. 285-294 (1997)

Kihara,M.：“血管紧张素原基因敲除小鼠的致密斑中，组成型一氧化氮合酶的神经元亚型上调。”