Genetic analyses reveal a requirement for Dicer1 in the mouse urogenital tract
Genetic analyses reveal a requirement for Dicer1 in the mouse urogenital tract
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DOI：
10.1007/s00335-008-9169-y
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发表时间：
2009-03-01
期刊：
影响因子：
2.5
通讯作者：
Greenfield, Andy
中科院分区：
文献类型：
--
作者：
Pastorelli, Laura M.;Wells, Sara;Greenfield, Andy
尽管人们对其他类型的小RNA越来越感兴趣，但microRNAs(MiRNAs)仍然是研究最广泛的，并已被证明在哺乳动物的许多不同过程中发挥作用。许多关于miRNA功能的研究都集中在加工酶Dicer1上，Dicer1是一种RNAseIII蛋白，它通过切割前体RNA分子而对活性miRNAs的生物发生至关重要。在小鼠中，Dicer1的普遍缺失证实了miRNAs对于发育是必不可少的，因为缺乏Dicer1的胚胎无法到达原肠发育的末端。在这里，我们研究Dicer1在泌尿生殖道发育中的作用。我们利用Dicer1基因的一个条件等位基因和两个由HoxB7和Amhr2驱动的Cre表达系来研究Dicer1缺失对雄性和雌性生殖道发育的影响。这里提供的数据强调了Dicer1在女性生殖道的正确形态发生和功能中的重要作用，并证实了最近的发现，表明Dicer1是女性生育所必需的。此外，HoxB7：Cre介导的输尿管芽衍生物缺失导致男性和女性的一系列异常，包括肾积水和肾实质囊肿。然而，在没有Dicer1的情况下，男性生殖道发育在很大程度上仍然没有受到影响。因此，Dicer1对于女性生殖道的发育和正常的肾脏形态发生都是必需的。
Despite the increasing interest in other classes of small RNAs, microRNAs (miRNAs) remain the most widely investigated and have been shown to play a role in a number of different processes in mammals. Many studies investigating miRNA function focus on the processing enzyme Dicer1, which is an RNAseIII protein essential for the biogenesis of active miRNAs through its cleavage of precursor RNA molecules. General deletion of Dicer1 in the mouse confirms that miRNAs are essential for development because embryos lacking Dicer1 fail to reach the end of gastrulation. Here we investigate the role of Dicer1 in urogenital tract development. We utilised a conditional allele of the Dicer1 gene and two Cre-expressing lines, driven by HoxB7 and Amhr2, to investigate the effect of Dicer1 deletion on both male and female reproductive tract development. Data presented here highlight an essential role for Dicer1 in the correct morphogenesis and function of the female reproductive tract and confirm recent findings that suggest Dicer1 is required for female fertility. In addition, HoxB7:Cre-mediated deletion in ureteric bud derivatives leads to a spectrum of anomalies in both males and females, including hydronephrotic kidneys and kidney parenchymal cysts. Male reproductive tract development, however, remains largely unaffected in the absence of Dicer1. Thus, Dicer1 is required for development of the female reproductive tract and also normal kidney morphogenesis.