Myocardial deletion of Smad4 using a novel α skeletal muscle actin Cre recombinase transgenic mouse causes misalignment of the cardiac outflow tract.
Myocardial deletion of Smad4 using a novel α skeletal muscle actin Cre recombinase transgenic mouse causes misalignment of the cardiac outflow tract.
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DOI：
10.7150/ijbs.6.546
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发表时间：
2010-09-20
影响因子：
9.2
通讯作者：
McLennan IS
中科院分区：
文献类型：
--
作者：
Azhar M;Wang PY;Frugier T;Koishi K;Deng C;Noakes PG;McLennan IS
SMAD 4在心脏发育中充当TGFβ和BMP信号传导的汇聚点。在此，我们使用新型α骨骼肌肌动蛋白Cre重组酶（MuCre）转基因小鼠品系研究SMAD 4在心脏发育中的作用。使用MuCre/ROSA 26 LacZ报告小鼠的谱系追踪表明，在发育和成年心脏和骨骼肌中有很强的Cre重组酶表达。在心脏发育中，在E11.5时，在心房、心室、流出道和房室管心肌中观察到显著的MuCre表达，但在内膜垫中没有。小鼠中MuCre驱动的Smad 4条件性缺失导致右心室双出口（DORV）、室间隔缺损（VSD）、心室肌小梁形成受损和变薄以及妊娠中期胚胎死亡。总之，MuCre小鼠有效地删除了心脏和骨骼肌中的基因，从而发现心肌Smad 4缺失导致流出道和DORV的错位。
SMAD4 acts as the converging point for TGFβ and BMP signaling in heart development. Here, we investigated the role of SMAD4 in heart development using a novel α skeletal muscle actin Cre recombinase (MuCre) transgenic mouse strain. Lineage tracing using MuCre/ROSA26LacZ reporter mice indicated strong Cre-recombinase expression in developing and adult heart and skeletal muscles. In heart development, significant MuCre expression was noted at E11.5 in the atrial, ventricular, outflow tract and atrioventricular canal myocardium, but not in the endocardial cushions. MuCre-driven conditional deletion of Smad4 in mice caused double outlet right ventricle (DORV), ventricular septal defect (VSD), impaired trabeculation and thinning of ventricular myocardium, and mid-gestational embryonic lethality. In conclusion, MuCre mice effectively delete genes in both heart and skeletal muscles, thus enabling the discovery that myocardial Smad4 deletion causes misalignment of the outflow tract and DORV.