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Functional Characteristics in the Embryo of Mouse Model of Transposition of the Great Arteries

大动脉转位小鼠胚胎模型的功能特征

基本信息

批准号：
06671172
负责人：
NAKAZAWA Makoto
金额：
$ 1.34万
依托单位：
Tokyo Women's Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671172/
关键词：
Cardiac Anomaly Mouse Embryo Retinoic Acid Transposition of the Great Arteries Hemodynamics

项目摘要

We had been trying to make a good model of transposition of the great arteries (TGA) in the mouse by treating pregnant dams by all-trans retinoic acid, and finally established the model in which TGA was induced in 90% of embryos by giving the drug with a dose of 70mg/kg at 8.5 days of gestation. Using this model, we have found that hypo-dysplasia of proximal outflow swelling causes failure of the normal ventriculo-arterial ralation and leads to parallel connection of the ventricles to the great arteries, i.e.the right ventricle (RV) to the aorta (Ao) and the left ventricle (LV) to the pulmonary artery (PA). We have then considered that it is important to find the role of hemodynamics in its morphogenesis, and established the technique in which the mammalian embryo is observed in situ under a microscope and action of the heart is recorded with a high speed video camera while it is still alive and viable. Using this method, it was found that there was two pattaerns of flow through outflow tract of the primitive ventricle in TGA model embryos ; one is that flow from RV to Ao was parallel to and separated from it from LV to PA ; the other was that flow from RV goes into both Ao and PA.The latter likely destined to TGA associated with malalign type ventricular septal defect, or double outlet right ventricle in an extreme case. Analysing the ventricular size and function, RV was smaller and lower in ejection fraction in TGA embryos than in controls, suggestings some possible role of hemodynamics in pathogenesis of TGA.

我们一直试图通过全反式维A酸治疗妊娠母鼠来建立良好的小鼠大动脉转位（TGA）模型，并最终在妊娠8.5天时给予70mg/kg剂量的药物，最终建立了90%胚胎中诱导TGA的模型。使用该模型，我们发现近端流出肿胀的发育不良会导致正常的心室-动脉关系失败，并导致心室与大动脉平行连接，即右心室（RV）与主动脉（Ao）和左心室（LV）与肺动脉（PA）平行连接。然后，我们认为找到血流动力学在其形态发生中的作用很重要，并建立了一种技术，在显微镜下原位观察哺乳动物胚胎，并在它仍然活着和有活力时用高速摄像机记录心脏的活动。利用该方法发现TGA模型胚胎的原始心室流出道存在两种血流模式；一是从RV到Ao的流量与从LV到PA的流量平行且分开；另一个是来自 RV 的血流同时进入 Ao 和 PA。后者可能注定会导致与排列不良型室间隔缺损相关的 TGA，或者在极端情况下导致右心室双出口。分析心室大小和功能，TGA 胚胎中的 RV 较小，射血分数低于对照组，这表明血流动力学在 TGA 发病机制中可能发挥一定作用。