Lrrc10 is required for early heart development and function in zebrafish
Lrrc10 is required for early heart development and function in zebrafish
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DOI：
10.1016/j.ydbio.2007.06.005
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发表时间：
2007-08-15
影响因子：
2.7
通讯作者：
Lee, Youngsook
中科院分区：
文献类型：
--
作者：
Kim, Ki-Hyun;Antkiewicz, Dagmara S.;Lee, Youngsook
富含亮氨酸重复序列的蛋白10(Lrrc10)最近被确定为小鼠的心脏特异因子。然而，该因子的作用仍有待阐明。在本研究中，我们以斑马鱼为动物模型，研究了Lrre 10的发育作用。在斑马鱼胚胎(变形体)中，使用rnorpholinos敲除lrrc 10基因会导致严重的心脏形态缺陷，包括心环衰竭并伴有巨大的心包水肿，以及受精后第6至7天的胚胎死亡。Lrrc 10变异体表现出心脏功能缺陷，表现为射血分数和心输出量的下降。对心脏缺陷的潜在机制的进一步研究表明，变异体中的心肌细胞数量减少。两个心脏基因的表达在变异体中被解除调控，包括心钠素的增加，这是心脏肥大和衰竭的标志，以及心肌肌球蛋白轻链2的减少，心肌肌球蛋白轻链2是斑马鱼心脏收缩能力的必要蛋白质。此外，与对照相比，在活斑马鱼胚胎中观察到形态心脏中NADH的荧光强度降低。综上所述，本研究表明Lrre 10是斑马鱼胚胎正常心脏发育和心脏功能所必需的，这将加深我们对先天性心脏病和心脏病的理解。(C)2007 Elsevier Inc.保留所有权利。
Leucine-rich Repeat Containing protein 10 (LRRC 10) has recently been identified as a cardiac-specific factor in mice. However, the function of this factor remains to be elucidated. In this study, we investigated the developmental roles of Lrre 10 using zebrafish as an animal model. Knockdown of Lrrc 10 in zebrafish embryos (morphants) using rnorpholinos caused severe cardiac morphogenic defects including a cardiac looping failure accompanied by a large pericardial edema, and embryonic lethality between day 6 and 7 post fertilization. The Lrrc 10 morphants exhibited cardiac functional defects as evidenced by a decrease in ejection fraction and cardiac output. Further investigations into the underlying mechanisms of the cardiac defects revealed that the number of cardiomyocyte was reduced in the morphants. Expression of two cardiac genes was deregulated in the morphants including an increase in atrial natriuretic factor, a hallmark for cardiac hypertrophy and failure, and a decrease in cardiac myosin light chain 2, an essential protein for cardiac contractility in zebrafish. Moreover, a reduced fluorescence intensity from NADH in the morphant heart was observed in live zebrafish embryos as compared to control. Taken together, the present study demonstrates that Lrre 10 is necessary for normal cardiac development and cardiac function in zebrafish embryos, which will enhance our understanding of congenital heart defects and heart disease. (c) 2007 Elsevier Inc. All rights reserved.