Ectopic expression of Cripto-1 in transgenic mouse embryos causes hemorrhages, fatal cardiac defects and embryonic lethality.
Ectopic expression of Cripto-1 in transgenic mouse embryos causes hemorrhages, fatal cardiac defects and embryonic lethality.
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转基因小鼠胚胎中 Cripto-1 的异位表达导致出血、致命性心脏缺陷和胚胎致死
DOI：
10.1038/srep34501
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发表时间：
2016-09-30
影响因子：
4.6
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Lin X;Zhao W;Jia J;Lin T;Xiao G;Wang S;Lin X;Liu Y;Chen L;Qin Y;Li J;Zhang T;Hao W;Chen B;Xie R;Cheng Y;Xu K;Yao K;Huang W;Xiao D;Sun Y
在小鼠中对Cripto - 1进行靶向破坏会在胚胎期第7.5天（E7.5）导致胚胎致死，然而我们意外地发现小鼠胚胎中异位表达Cripto - 1也会导致胚胎致死，这促使我们去描述因Cripto - 1异位表达导致胚胎死亡的原因和潜在机制。RCLG/EIIa - Cre胚胎在胚胎期第14.5天（E14.5）到第17.5天（E17.5）之间表现出复杂的表型，包括致命性出血（E14.5 - E15.5）、胚胎吸收（E14.5 - E17.5）、体表苍白（E14.5 - E16.5）以及无异常外观（E14.5 - E16.5）。宏观和组织学检查显示，在RCLG/EIIa - Cre胚胎中Cripto - 1转基因的异位表达导致了致命的心脏缺陷，心脏畸形、心肌变薄、横纹肌原纤维组装失败以及无心跳都证明了这一点。此外，在E8.5之后开始的Cripto - 1转基因激活也在小鼠胚胎中导致了上述致命的心脏缺陷。再者，胚胎心脏中Cripto - 1的异位表达降低了心脏转录因子的表达，这至少部分地导致了上述致命的心脏缺陷。我们的结果表明出血和心脏异常是Cripto - 1转基因小鼠中两个重要的致死因素。综上所述，这些发现首次证明在E11.5之后持续的Cripto - 1转基因表达会导致致命性出血和致命的心脏缺陷，从而在E14.5 - 17.5导致胚胎死亡。
Targeted disruption of Cripto-1 in mice caused embryonic lethality at E7.5, whereas we unexpectedly found that ectopic Cripto-1 expression in mouse embryos also led to embryonic lethality, which prompted us to characterize the causes and mechanisms underlying embryonic death due to ectopic Cripto-1 expression. RCLG/EIIa-Cre embryos displayed complex phenotypes between embryonic day 14.5 (E14.5) and E17.5, including fatal hemorrhages (E14.5-E15.5), embryo resorption (E14.5-E17.5), pale body surface (E14.5-E16.5) and no abnormal appearance (E14.5-E16.5). Macroscopic and histological examination revealed that ectopic expression of Cripto-1 transgene in RCLG/EIIa-Cre embryos resulted in lethal cardiac defects, as evidenced by cardiac malformations, myocardial thinning, failed assembly of striated myofibrils and lack of heartbeat. In addition, Cripto-1 transgene activation beginning after E8.5 also caused the aforementioned lethal cardiac defects in mouse embryos. Furthermore, ectopic Cripto-1 expression in embryonic hearts reduced the expression of cardiac transcription factors, which is at least partially responsible for the aforementioned lethal cardiac defects. Our results suggest that hemorrhages and cardiac abnormalities are two important lethal factors in Cripto-1 transgenic mice. Taken together, these findings are the first to demonstrate that sustained Cripto-1 transgene expression after E11.5 causes fatal hemorrhages and lethal cardiac defects, leading to embryonic death at E14.5-17.5.
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影响因子：
--
作者：
Lin X;Jia J;Qin Y;Lin X;Li W;Xiao G;Li Y;Xie R;Huang H;Zhong L;Wu Q;Wang W;Huang W;Yao K;Xiao D;Sun Y
通讯作者：
Sun Y