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Prkra中的点突变在胚胎外耳发育过程中改变miRNA表达。

Point Mutation in Prkra Alters miRNA Expression During Embryonic External Ear Development.

作者信息

Liu Wei, Lin Lin, Yang Qinghua, Jin Shengyang, Jiang Haiyue

机构信息

Plastic Surgery Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100144, China.

出版信息

J Craniofac Surg. 2023;34(2):777-784. doi: 10.1097/SCS.0000000000008837. Epub 2022 Aug 15.

Abstract

Microtia is a congenital malformation of the external ear that can lead to conductive hearing impairment. In this study, we investigated the role of the Prkra gene in external ear development. We used advanced sequencing techniques to evaluate the differential expression of microRNAs (miRNAs) involved in external ear development in mouse embryos after point mutation in the Prkra gene. The Prkra Little ear mouse model was used to obtain mouse embryos at the E15.5 and E17.5 developmental stages, and changes in miRNA expression profiles were detected. Gene ontology and Kyoto Encyclopedia of Genes and Genomes functional annotations were performed on differentially expressed miRNAs, and existing and new miRNAs were studied. miRNAs were observed to be involved in multiple signaling pathways during the E15.5 and E17.5 developmental stages. The results show a correlation between miRNA regulation and external ear development in Prkra Little ear mice, and differences were detected in key regulatory miRNAs owing to point mutations in the Prkra gene. This study provides new insights into the biological mechanisms through which miRNAs regulate external ear development in mouse embryos. Changes in the mouse miRNA expression profiles can also provide insights into the pathogenesis of human congenital microtia at the level of miRNA regulation.

摘要

小耳畸形是一种外耳先天性畸形,可导致传导性听力障碍。在本研究中,我们调查了Prkra基因在外耳发育中的作用。我们使用先进的测序技术来评估Prkra基因突变后小鼠胚胎中外耳发育相关微小RNA(miRNA)的差异表达。利用Prkra小耳小鼠模型获取处于E15.5和E17.5发育阶段的小鼠胚胎,并检测miRNA表达谱的变化。对差异表达的miRNA进行基因本体论和京都基因与基因组百科全书功能注释,并研究已知和新的miRNA。观察到miRNA在E15.5和E17.5发育阶段参与多个信号通路。结果显示Prkra小耳小鼠中miRNA调控与外耳发育之间存在相关性,并且由于Prkra基因突变,关键调控miRNA存在差异。本研究为miRNA调控小鼠胚胎外耳发育的生物学机制提供了新见解。小鼠miRNA表达谱的变化也可以在miRNA调控水平上为人类先天性小耳畸形的发病机制提供见解。

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