Paulus Jeremiah D, Link Brian A
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, United States of America.
PLoS One. 2014 Oct 16;9(10):e109922. doi: 10.1371/journal.pone.0109922. eCollection 2014.
Mutations in Optineurin have been associated with ALS, glaucoma, and Paget's disease of bone in humans, but little is known about how these mutations contribute to disease. Most of the cellular consequences of Optineurin loss have come from in vitro studies, and it remains unclear whether these same defects would be seen in vivo. To answer this question, we assessed the cellular consequences of Optineurin loss in zebrafish embryos to determine if they showed the same defects as have been described in the in vitro studies. We found that loss of Optineurin resulted in increased cell death, as well as subtle cell morphology, cell migration and vesicle trafficking defects. However, unlike experiments on cells in culture, we found no indication that the Golgi apparatus was disrupted or that NF-κB target genes were upregulated. Therefore, we conclude that in vivo loss of Optineurin shows some, but not all, of the defects seen in in vitro work.
在人类中，视紫质（Optineurin）的突变与肌萎缩侧索硬化症（ALS）、青光眼和佩吉特骨病相关，但对于这些突变如何导致疾病却知之甚少。视紫质缺失的大多数细胞后果来自体外研究，目前尚不清楚这些相同的缺陷在体内是否也会出现。为了回答这个问题，我们评估了斑马鱼胚胎中视紫质缺失的细胞后果，以确定它们是否表现出与体外研究中描述的相同缺陷。我们发现，视紫质的缺失导致细胞死亡增加，以及细微的细胞形态、细胞迁移和囊泡运输缺陷。然而，与细胞培养实验不同的是，我们没有发现高尔基体被破坏或核因子κB（NF-κB）靶基因上调的迹象。因此，我们得出结论，视紫质在体内的缺失表现出了一些（但不是全部）体外研究中所见的缺陷。
