Loss of function of axonemal dynein Mdnah5 causes primary ciliary dyskinesia and hydrocephalus
Loss of function of axonemal dynein Mdnah5 causes primary ciliary dyskinesia and hydrocephalus
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DOI：
10.1093/hmg/11.6.715
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发表时间：
2002-03-15
影响因子：
3.5
通讯作者：
Heintz, N
中科院分区：
文献类型：
--
作者：
Ibañez-Tallon, I;Gorokhova, S;Heintz, N
原发性纤毛运动障碍（PCD），也称为Kartagener综合征，是由纤毛功能障碍引起的人类综合征。这种综合征的特征是反复呼吸道感染、内脏逆位和不孕。在某些情况下，还观察到脑积水。我们已经表征了小鼠轴丝动力蛋白重链基因（Mdnah5）中的插入突变，该基因再现了PCD的大多数经典特征，包括反复呼吸道感染、逆位和纤毛不动性。这些小鼠也患有脑积水并在围产期死亡。电子显微镜研究表明轴丝外臂的损失。这些结果表明，Mdnah5突变是PCD的主要原因，并提供了直接证据表明，轴丝动力蛋白突变可导致脑积水。最近在PCD患者中鉴定了人DNAH5的突变。小鼠模型和人类数据的比较表明，纤毛功能障碍的程度与人类PCD的严重程度有因果关系，特别是脑积水的存在。
Primary ciliary dyskinesia (PCD), also known as Kartagener's syndrome, is a human syndrome that results from ciliary dysfunction. This syndrome is characterized by recurrent respiratory infections, situs inversus and infertility. In some cases, hydrocephalus is also observed. We have characterized an insertional mutation in a mouse axonemal dynein heavy chain gene (Mdnah5) that reproduces most of the classical features of PCD, including recurrent respiratory infections, situs inversus and ciliary immotility. These mice also suffer from hydrocephalus and die perinatally. Electron microscopic studies demonstrate the loss of axonemal outer arms. These results show that mutations in Mdnah5 are a primary cause of PCD and provide direct evidence that mutations in an axonemal dynein can cause hydrocephalus. Mutations in the human DNAH5 have recently been identified in PCD patients. Comparison of the mouse model and the human data suggests that the degree of ciliary dysfunction is causally related to the severity of human PCD, particularly the presence of hydrocephalus.