- 著者
-
Cao Qing
Pu Jielin
Hong Kui
Shen Yang
Liu Xin
Yu Xin
Yuan Ping
Wan Rong
Liu Xiuxia
Peng Xiaogang
He Wenfeng
- 出版者
- 一般社団法人 インターナショナル・ハート・ジャーナル刊行会
- 雑誌
- International Heart Journal (ISSN:13492365)
- 巻号頁・発行日
- vol.58, no.6, pp.939-947, 2017
- 被引用文献数
-
20
<p><i>DTNA</i> encoding dystrobrevin-α (α-DB) is a putative causal gene associated with left ventricular noncompaction cardiomyopathy (LVNC). The aim of the study was to investigate the causal role of DTNA in LVNC using a transgenic mouse model.</p><p>A missense mutation (c.146A > G, p.N49S) of <i>DTNA</i> was identified in a patient with LVNC by Sanger sequencing. Six independent lines of transgenic mice expressing the mutant DTNA under a myosin heavy chain 6 (<i>Myh6</i>) promoter were generated (<i>Myh6:Dtna</i><sup><i>N49S</i></sup>). Phenotypic characteristics of <i>DTNA</i>-p.N49S mutations were evaluated by echocardiography, histological observation, and immunoblotting. Multiple trabeculation and a higher ratio of non-compacted to compact myocardial layer were found in the <i>Myh6:Dtna</i><sup><i>N49S</i></sup> mice compared to the controls. The transgenic mice also showed left ventricular (LV) dilation and cardiac systolic dysfunction. In conclusion, overexpression of the <i>DTNA</i>-p.N49S mutation in a mouse heart can be responsible for the phenotype of deep trabeculation, dilated cardiomyopathy, and cardiac dysfunction, which resembles the phenotype of LVNC.</p>