Stabilised beta-catenin in postnatal ventricular myocardium leads to dilated cardiomyopathy and premature death
Stabilised beta-catenin in postnatal ventricular myocardium leads to dilated cardiomyopathy and premature death
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DOI：
10.1007/s00395-010-0101-8
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发表时间：
2010-09-01
影响因子：
9.5
通讯作者：
Ehler, Elisabeth
中科院分区：
文献类型：
--
作者：
Hirschy, Alain;Croquelois, Adrien;Ehler, Elisabeth
β-连环蛋白是心肌细胞间盘的一种成分，但也可以参与基因转录的信号传递和激活。我们想要确定β-连环蛋白表达水平的长期变化将如何影响成熟的心肌细胞。条件转基因小鼠要么缺乏β-连环素，要么在成年脑室表达不可降解的β-连环素。虽然在脑室缺乏β-连环素的小鼠没有明显的表型，但表现为不可降解形式的小鼠患上扩张型心肌病，存活时间不超过5个月。一项详细的分析可以揭示，这种表型与β-连环素在成年心肌细胞中的独特定位有关，无论存在多少蛋白质，都无法在细胞核中检测到这种定位。我们的报告是第一个研究缺乏β-连环蛋白或其稳定对心室肌细胞的长期影响的研究，它表明，在健康的成年人心脏中，β-连环蛋白在细胞核中的作用可能没有什么意义。
Beta-catenin is a component of the intercalated disc in cardiomyocytes, but can also be involved in signalling and activation of gene transcription. We wanted to determine how long-term changes in beta-catenin expression levels would affect mature cardiomyocytes. Conditional transgenic mice that either lacked beta-catenin or that expressed a non-degradable form of beta-catenin in the adult ventricle were created. While mice lacking beta-catenin in the ventricle do not have an overt phenotype, mice expressing a non-degradable form develop dilated cardiomyopathy and do not survive beyond 5 months. A detailed analysis could reveal that this phenotype is correlated with a distinct localisation of beta-catenin in adult cardiomyocytes, which cannot be detected in the nucleus, no matter how much protein is present. Our report is the first study that addresses long-term effects of either the absence of beta-catenin or its stabilisation on ventricular cardiomyocytes and it suggests that beta-catenin's role in the nucleus may be of little significance in the healthy adult heart.