pitx2 function in morphogenesis of atrioventricular septal defect in heart

pitx2在心脏房室间隔缺损形态发生中的作用

• 批准号: 12670782
• 负责人: MIYAGAWA Sachiko
• 金额: $ 2.05万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670782/
• 关键词: congenital heart defect; development; pitx2 gene; atrioventricular septal defect; morphogenesis; mouse embryo; pitx2遺伝子; 心臓発生; Pitx2; 心臓

Atrioventricular septal defect (AVSD) is a malformation of the heart that results from failure of normal septation of the ventricular inlet. Molecular studies of AVSD have proposed some candidate genes, however, the function of these genes remains unclear. The morphological mechanism of AVSD is complex and not well understood. A common atrioventricular valve was found in our generated Pitx2-deficient mice, which is similar to the complete type of atrioventricular septal defect in human.Atrioventricular cushions showed normal function of adherence in vitro and many mesenchymal cells histologically. Pitx2 was expressed in the left sinus venosus at the early stage embryo, and then the expression shifted to the left side of the right atrium. In Pitx2-deficient mice, the expression did not shift and Pitx2 was expressed in the right side of the left atrium. These results suggest that the left sinus venosus plays an important role in the morphogenesis of atrioventricular septal defect.

房室间隔缺损(AVSD)是一种心脏畸形，由室口正常间隔失败引起。房间隔缺损的分子生物学研究已经提出了一些候选基因，但这些基因的功能尚不清楚。房室间隔缺损的形态机制复杂，目前尚不清楚。在我们产生的PITX2基因缺陷小鼠身上发现了一种常见的房室瓣，类似于人类完全型房室间隔缺损。体外房室垫显示正常的黏附功能，组织学上可见大量间充质细胞。胚胎早期，Pitx2在左侧静脉窦有表达，之后转移到右心房左侧。在Pitx2基因缺陷的小鼠中，该基因的表达没有改变，并且在左心房的右侧表达。这些结果提示，左窦静脉在房室间隔缺损的形态发生中起重要作用。

项目成果

Miyagawa-Tomita S, Yanazawa M, Ohmichi K, Nakazawa M, Kitamura K: "pitx2 gene function in cardiac morphogenesis in mice."Etiology and morphogenesis of congenital cardiovascular disease in the post-genomic era, Tokyo, Japan. 138-139 (2002)

Miyakawa-Tomita S、Yanazawa M、Ohmichi K、Nakazawa M、Kitamura K：“pitx2 基因在小鼠心脏形态发生中的功能。”后基因组时代先天性心血管疾病的病因学和形态发生，日本东京。

Kokubo H, Miyagawa-Tomita S, Tomimatsu H, Nakazawa M, Johnson RL, Saga Y: "hesr genes in cardiogenesis."25th Mol Biol Society Jpn, Yokohama, Japan. W4aM. (2002)

Kokubo H、Miyakawa-Tomita S、Tomimatsu H、Nakazawa M、Johnson RL、Saga Y：“心脏发生中的 hesr 基因”。第 25 届 Mol Biol Society Jpn，日本横滨。

Shinohara T, Tomita H, Nakazawa M, Miyagawa-Tomita S: "Role of the cardiac neural crest in the outflow tract of the developing heart."Reports of the Research Institute, Saitama Cardiovascular and Respiratory Center. 5. 22-24 (2001)

Shinohara T、Tomita H、Nakazawa M、Miyakawa-Tomita S：“心脏神经嵴在发育中的心脏流出道中的作用。”埼玉心血管和呼吸中心研究所的报告。

Takeuchi T, Miyagawa-Tomita S, Nakazawa M: "The mechanisms of cell proliferation during cardiac development and regeneration."Japan Research Promotion Society for Cardiovascular Diseases. 16. 11-14 (2001)

Takeuchi T、Miyakawa-Tomita S、Nakazawa M：“心脏发育和再生过程中细胞增殖的机制。”日本心血管疾病研究促进会。

Saga Y, Kitajima S, Miyagawa-Tomita S: "Mesp1 expression is the earliest sign of cardiovascular development"Trend Cardiovasc Med. 10(8). 345-352 (2000)

Saga Y、Kitajima S、Miyakawa-Tomita S：“Mesp1 表达是心血管发育的最早标志”Trend Cardiovasc Med。