PUBLICATION
Nicastrin Deficiency Induces Tyrosinase-dependent Depigmentation and Skin Inflammation
- Authors
- Hsu, C.H., Liou, G.G., Jiang, Y.J.
- ID
- ZDB-PUB-190823-12
- Date
- 2019
- Source
- The Journal of investigative dermatology 140(2): 404-414.e13 (Journal)
- Registered Authors
- Hsu, Chia-Hao, Jiang, Yun-Jin
- Keywords
- none
- MeSH Terms
-
- Amyloid Precursor Protein Secretases/genetics*
- Amyloid Precursor Protein Secretases/metabolism
- Animals
- Animals, Genetically Modified
- Disease Models, Animal
- Embryo, Nonmammalian
- Humans
- Hypopigmentation/genetics*
- Hypopigmentation/immunology
- Hypopigmentation/pathology
- Melanosomes/immunology
- Melanosomes/metabolism
- Melanosomes/ultrastructure
- Membrane Glycoproteins/genetics*
- Membrane Glycoproteins/metabolism
- Microscopy, Electron, Transmission
- Monophenol Monooxygenase/antagonists & inhibitors
- Monophenol Monooxygenase/genetics
- Monophenol Monooxygenase/metabolism*
- Mutation
- Skin/immunology*
- Skin/pathology
- Skin Pigmentation/drug effects
- Skin Pigmentation/genetics
- Zebrafish
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 31437444 Full text @ J. Invest. Dermatol.
Citation
Hsu, C.H., Liou, G.G., Jiang, Y.J. (2019) Nicastrin Deficiency Induces Tyrosinase-dependent Depigmentation and Skin Inflammation. The Journal of investigative dermatology. 140(2):404-414.e13.
Abstract
Skin depigmentation diseases, such as vitiligo, are pigmentation disorders that often destroy melanocytes. However, their pathological mechanisms remain unclear and, therefore, promising treatments or prevention have been lacking. Here we demonstrate that a zebrafish insertional mutant showing a significant reduction of nicastrin transcript possesses melanosome maturation defect, Tyrosinase-dependent mitochondrial swelling and melanophore cell death. The depigmentation phenotypes are proven to be a result of γ-secretase inactivation. Furthermore, live imaging demonstrates that macrophages are recruited to and can phagocytose melanophore debris. Thus, we characterize a potential zebrafish depigmentation disease model, nicastrinhi1384 mutants, which can be used for further treatment/drug development of diseases related to skin depigmentation and/or inflammation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping