Inactivation of the Sema5a gene results in embryonic lethality and defective remodeling of the cranial vascular system
Inactivation of the Sema5a gene results in embryonic lethality and defective remodeling of the cranial vascular system
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DOI：
10.1128/mcb.25.6.2310-2319.2005
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发表时间：
2005-03-01
影响因子：
5.3
通讯作者：
Püschell, AW
中科院分区：
文献类型：
--
作者：
Fiore, R;Rahim, B;Püschell, AW
脑信号蛋白是一个大家族的蛋白质参与的模式的血管和神经系统。为了分析膜结合脑信号蛋白5A（Sema5A）的功能，我们产生了Sema5a基因无效突变的纯合子小鼠。纯合无效突变体在胚胎发育第11.5天（E11.5）和E12.5之间死亡，表明Sema5A在胚胎发育过程中起重要作用。突变胚胎没有表现出任何可以解释突变致死性的形态缺陷。对血管系统的详细分析揭示了Sema5A在颅血管重塑中的作用。在Sema5A无效突变体中，颅主静脉的分层组织分支的复杂性降低。我们的研究结果代表了第一个5类semaphorin在胚胎发育过程中的功能的遗传分析，并确定了Sema5A的区域模式的脉管系统中的作用。
The semaphorins are a large family of proteins involved in the patterning of both the vascular and the nervous systems. In order to analyze the function of the membrane-bound semaphorin 5A (Sema5A), we generated mice homozygous for a null mutation in the Sema5a gene. Homozygous null mutants die between embryonic development days 11.5 (E11.5) and E12.5, indicating an essential role of Sema5A during embryonic development. Mutant embryos did not show any morphological defects that could account for the lethality of the mutation. A detailed analysis of the vascular system uncovered a role of Sema5A in the remodeling of the cranial blood vessels. In Sema5A null mutants, the complexity of the hierarchically organized branches of the cranial cardinal veins was decreased. Our results represent the first genetic analysis of the function of a class 5 semaphorin during embryonic development and identify a role of Sema5A in the regional patterning of the vasculature.