國家衛生研究院 NHRI:Item 3990099045/10596

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Title:	Zebrafish nicastrin deficiency leads to a Tyrosinase-dependent depigmentation
Authors:	Hsu, CH;Jiang, YJ
Contributors:	Institute of Molecular and Genomic Medicine
Abstract:	Notch is a highly conserved signaling pathway involving in adjacent cell regulations, such as differentiation, proliferation and apoptosis. The perturbation of the signaling pathway is associated with cardiac diseases, intrahepatic bile duct paucity, inﬂammatory diseases, and also skeletal patterning defects. Recently, suppressing of Notch signaling by γ-secretase inhibitor was also found to alter the patterning of melanocytes on adult zebraﬁsh and induce hair graying on mice with mechanism remained largely unknown. To understand the potential role of γ-secretase in pigment regulation, nicastrin hi1384 , which has an insertional mutation on one of theγ-secretase components, was employed. Here we found that, the nicastrin hi1384 mutant, which has a GT2.0 virus insertion in the intron one region and, therefore, loses the expression of nicastrin mRNA, showed hypopigmentation and curly up tail phenotypes. Besides, the phenotypes can be partially mimicked or rescued in morpholino knockdown experiments and nicastrin mRNA overexpression, respectively. With live image observation and whole mount in situ hybridization, the melanocytes and eye iridophores were found gradually losing in the homozygotes. The cone and rod cells were also vanishing in the progression of depigmentation according to H&E staining. Through literature research, we were suspecting that the depigmentation might be caused by toxic components, including Eumelanin and ROS, produced by Tyrosinase. The Tyrosinase inhibitor and ROS inhibitor were, therefore, applied to test the hypothesis, and the results suggest that Eumelanin could be the toxic component to induce Vitiligo in the nicastrin mutant.
Date:	2017-07
Relation:	Mechanisms of Development. 2017 Jul;145(Suppl.):S99.
Link to:	https://doi.org/10.1016/j.mod.2017.04.255
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000402994800328
Appears in Collections:	[Yun-Jin Jiang] Conference Papers/Meeting Abstract

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