Neuroscience Program, Lafayette College, Easton, Pennsylvania, United States of America.
PLoS One. 2021 Apr 1;16(4):e0246844. doi: 10.1371/journal.pone.0246844. eCollection 2021.
Multiple cilia-associated genes have been shown to affect hair cells in zebrafish (Danio rerio), including the human deafness gene dcdc2, the radial spoke gene rsph9, and multiple intraflagellar transport (IFT) and transition zone genes. Recently a zebrafish alms1 mutant was generated. The ALMS1 gene is the gene mutated in the ciliopathy Alström Syndrome a disease that causes hearing loss among other symptoms. The hearing loss seen in Alström Syndrome may be due in part to hair cell defects as Alms1 mutant mice show stereocilia polarity defects and a loss of hair cells. Hair cell loss is also seen in postmortem analysis of Alström patients. The zebrafish alms1 mutant has metabolic defects similar to those seen in Alström syndrome and Alms1 mutant mice. We wished to investigate if it also had hair cell defects. We, however, failed to find any hair cell related phenotypes in alms1 mutant zebrafish. They had normal lateral line hair cell numbers as both larvae and adults and normal kinocilia formation. They also showed grossly normal swimming behavior, response to vibrational stimuli, and FM1-43 loading. Mutants also showed a normal degree of sensitivity to both short-term neomycin and long-term gentamicin treatment. These results indicate that cilia-associated genes differentially affect different hair cell types.
已经有多个与纤毛相关的基因被证明会影响斑马鱼（Danio rerio）的毛细胞，包括人类耳聋基因 dcdc2、辐条基因 rsph9 以及多个内鞭毛运输（IFT）和过渡区基因。最近，一种斑马鱼 alms1 突变体被生成。ALMS1 基因是纤毛病 Alström 综合征中突变的基因，该病会导致听力损失等症状。Alström 综合征中观察到的听力损失部分可能是由于毛细胞缺陷，因为 Alms1 突变小鼠显示出静纤毛极性缺陷和毛细胞缺失。Alström 患者的尸检分析也显示了毛细胞的缺失。斑马鱼 alms1 突变体具有与 Alström 综合征和 Alms1 突变小鼠相似的代谢缺陷。我们希望研究它是否也存在毛细胞缺陷。然而，我们未能在 alms1 突变体斑马鱼中发现任何与毛细胞相关的表型。它们在幼虫和成年期都具有正常的侧线毛细胞数量和正常的纤毛形成。它们的游泳行为、对振动刺激的反应和 FM1-43 加载也表现出明显的正常。突变体对短期新霉素和长期庆大霉素处理的敏感性也正常。这些结果表明，纤毛相关基因对不同的毛细胞类型有不同的影响。
