Makrogkikas Stylianos, Cheng Ruey-Kuang, Lu Hao, Roy Sudipto
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
J Neurogenet. 2023 Sep;37(3):85-92. doi: 10.1080/01677063.2023.2187792. Epub 2023 Mar 24.
is predicted to encode a very large type-I transmembrane protein, but its function has largely remained obscure. Recently, it was shown that Pkhdl1l1 is a component of the coat that decorates stereocilia of outer hair cells in the mouse ear. Consistent with this localization, conditional deletion of specifically from hair cells, was associated with progressive hearing loss. In the zebrafish, there are two paralogous genes - and Using CRISPR-Cas9 mediated gene editing, we generated loss-of-function alleles for both and show that the double mutants exhibit nonsense-mediated-decay (NMD) of the RNAs. With behavioural assays, we demonstrate that zebrafish genes also regulate hearing; however, in contrast to mutant mice, which develop progressive hearing loss, the double mutant zebrafish exhibited statistically significant hearing loss even from the larval stage. Our data highlight a conserved function of in hearing and based on these findings from animal models, we postulate that could be a candidate gene for sensorineural hearing loss (SNHL) in humans.
预计它编码一种非常大的I型跨膜蛋白，但其功能在很大程度上仍不清楚。最近研究表明，Pkhdl1l1是装饰小鼠耳朵外毛细胞静纤毛的衣被的一个组成部分。与这种定位一致，特异性地从毛细胞中条件性缺失该基因与进行性听力损失有关。在斑马鱼中，有两个同源基因—— 和 。利用CRISPR-Cas9介导的基因编辑，我们为这两个基因都生成了功能缺失等位基因，并表明双突变体表现出RNA的无义介导衰变（NMD）。通过行为分析，我们证明斑马鱼 基因也调节听力；然而，与出现进行性听力损失的 突变小鼠不同，双突变斑马鱼即使在幼虫阶段就表现出具有统计学意义的听力损失。我们的数据突出了 在听力方面的保守功能，基于动物模型的这些发现，我们推测 可能是人类感音神经性听力损失（SNHL）的一个候选基因。
