Mutation of Murine Adenylate Kinase 7 Underlies a Primary Ciliary Dyskinesia Phenotype
Mutation of Murine Adenylate Kinase 7 Underlies a Primary Ciliary Dyskinesia Phenotype
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DOI：
10.1165/rcmb.2008-0102oc
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发表时间：
2009-03-01
影响因子：
6.4
通讯作者：
Mitsialis, S. Alex
中科院分区：
文献类型：
--
作者：
Fernandez-Gonzalez, Angeles;Kourembanas, Stella;Mitsialis, S. Alex
原发性纤毛运动障碍（PCD）是一种遗传性和表型异质性疾病，其特征是进行性发展的支气管扩张、炎症和慢性阻塞性肺病的特征。我们在这里报告，小鼠突变的进化保守的腺苷酸激酶7（Ak7）基因的结果在动物中表现出病理学特征的PCD，包括超微结构的纤毛缺陷和呼吸上皮纤毛跳动频率降低的迹象。该突变与脑积水、精子发生异常、鼻旁通道粘液积聚和过敏原激发后显著的呼吸道病理学有关。Ak7似乎是具有（9 + 2）微管组织的纤毛的标志物。这是由其表达的组织特异性以及Ak7直系同源物结构仅在具有能动（9 + 2）纤毛的原生动物和后生动物中的严格保守性所暗示的。总的来说，我们的研究结果表明，祖先和至关重要的作用，Ak7在维持纤毛结构和功能，并表明，人类直系同源物的突变可能是一个子集的遗传特征不明的PCD情况下。
Primary ciliary dyskinesia (PCD) is a genetically and phenotypically heterogeneous disorder, characterized by progressive development of bronchiectasis, inflammation, and features characteristic of chronic obstructive pulmonary disease. We report here that a murine mutation of the evolutionarily conserved adenylate kinase 7 (Ak7) gene results in animals presenting with pathological signs characteristic of PCD, including ultrastructural ciliary defects and decreased ciliary beat frequency in respiratory epithelium. The mutation is associated with hydrocephalus, abnormal spermatogenesis, mucus accumulation in paranasal passages, and a dramatic respiratory pathology upon allergen challenge. Ak7 appears to be a marker for cilia with (9 + 2) microtubular organization. This is suggested by its tissue specificity of expression and also the stringent conservation of Ak7 ortholog structure only in protozoans and metazoans possessing motile (9 + 2) cilia. Collectively, our results indicate an ancestral and crucial role of Ak7 in maintaining ciliary structure and function, and suggest that mutations of the human ortholog may underlie a subset of genetically uncharacterized PCD cases.