Congenital diaphragmatic hernia, kidney agenesis and cardiac defects associated with Slit3-deficiency in mice
Congenital diaphragmatic hernia, kidney agenesis and cardiac defects associated with Slit3-deficiency in mice
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DOI：
10.1016/s0925-4773(03)00161-8
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发表时间：
2003-09-01
影响因子：
2.6
通讯作者：
Hu, HY
中科院分区：
文献类型：
--
作者：
Liu, JM;Zhang, L;Hu, HY
Slit3与Slit1和Slit2组成了Slit蛋白家族。后两种蛋白在动物发育过程中参与轴突引导和细胞迁移。然而，我们对Slit3的功能知之甚少。我们利用OmniBank ES细胞系，通过插入诱变捕获一个Slit3等位基因，建立了一个Slit3缺陷小鼠模型，以分析该蛋白在体内的功能。在本模型中，先天性膈疝是最明显的表型。发现疝是由膈肌中央肌腱（CT）的缺陷引起的，它仍然与肝脏融合。缺陷CT的电镜分析显示胶原原纤维组织紊乱，无法形成紧密的胶原束。slit3缺陷小鼠的心脏右心室增大。此外，20%的纯合子小鼠还表现出一系列肾脏缺陷，包括单侧或双侧肾脏和输尿管发育不全，或不同程度的肾发育不全。因此，我们得出结论，Slit3参与了包括横膈膜和肾脏在内的多个器官系统的发育。slit3缺陷小鼠是先天性膈疝生理和病理研究的遗传动物模型。2003爱思唯尔爱尔兰有限公司版权所有。
Slit3 along with Slit1 and Slit2 comprise the Slit family of proteins. The latter two proteins are known to be involved in axon guidance and cell migration during animal development. However, little is know about the functions of Slit3. We created a Slit3-deficient mouse model from an OmniBank ES cell line with a Slit3 allele trapped by insertional mutagenesis to analyze the in vivo functions of this protein. In this model, congenital diaphragmatic hernia is the most obvious phenotype. Herniation was found to be caused by a defective central tendon (CT) of the diaphragm that remained fused with the liver. Electron microscopic analyses of the defective CT revealed disorganized collagen fibrils that failed to form tight collagen bundles. The hearts of Slit3-deficient mice have an enlarged right ventricle. In addition, 20% of homozygous mice also showed a range of kidney defects that include unilateral or bilateral agenesis of the kidney and ureter, or varying degrees of renal hypoplasia. Thus, we concluded that Slit3 is involved in the development of multiple organ systems that include the diaphragm and the kidney. Slit3-deficient mice represent a genetic animal model for physiological and pathological studies of congenital diaphragmatic hernia. (C) 2003 Elsevier Ireland Ltd. All rights reserved.