Abstract
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.
Highlights
Optineurin (OPTN) has been associated with a number of different diseases
Amyotrophic lateral sclerosis (ALS) is a progressive debilitating condition where the loss of spinal motor neurons leads to paralysis and death, and researchers have found mutations in OPTN to be associated with various forms of this disease [21,22,23,24,25,26,27,28,29,30,31,32,33,34,35]
We found that all the major axon tracts at these ages appeared normal with no observable defects in axon extension, branching or pathfinding of the anterior commissure (AC), post-optic commissure (POC), posterior commissure (PC), dorsal longitudinal fasciculus (DLF) and medial longitudinal fasciculus (MLF) (Fig. 7A, B)
Summary
Optineurin (OPTN) has been associated with a number of different diseases. Subsequent groups have implicated many different mutations in OPTN with this disease [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]. Amyotrophic lateral sclerosis (ALS) is a progressive debilitating condition where the loss of spinal motor neurons leads to paralysis and death, and researchers have found mutations in OPTN to be associated with various forms of this disease [21,22,23,24,25,26,27,28,29,30,31,32,33,34,35]. OPTN has been associated with all of these diseases, it is still not known how mutations in OPTN contribute to the disease pathology
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