AP-3 complex delta subunit gene, ap3d1, regulates melanogenesis and melanophore survival via autophagy in zebrafish (Danio rerio)
- Neuffer, S.J., Beltran-Cardona, D., Jimenez-Perez, K., Clancey, L.F., Brown, A., New, L., Cooper, C.D.
- Pigment cell & melanoma research 35(5): 495-505 (Journal)
- Registered Authors
- Cooper, Cynthia
- Hermanksy-Pudlak Syndrome, albinism, cell survival, differentiation, specification
- MeSH Terms
- Carrier Proteins/genetics
- Hermanski-Pudlak Syndrome*/genetics
- 35816398 Full text @ Pigment Cell Melanoma Res.
Neuffer, S.J., Beltran-Cardona, D., Jimenez-Perez, K., Clancey, L.F., Brown, A., New, L., Cooper, C.D. (2022) AP-3 complex delta subunit gene, ap3d1, regulates melanogenesis and melanophore survival via autophagy in zebrafish (Danio rerio). Pigment cell & melanoma research. 35(5):495-505.
Zebrafish are an emerging model organism to study syndromic albinism disorder, Hermansky-Pudlak syndrome due to visible pigment development at 24 hours post fertilization, and conserved melanogenesis mechanisms. We describe crasher, a novel HPS type 10 (HPS10) zebrafish model, with a mutation in AP-3 complex delta subunit, ap3d1. Exon 14 of ap3d1 is overexpressed in crasher mutants, while the expression of ap3d1 as a whole is reduced. ap3d1 knockout in *AB zebrafish recapitulates the mutant crasher phenotype. We show ap3d1 loss-of-function mutations cause significant expression changes in the melanogenesis genes, dopachrome tautomerase (dct) and tyrosinase-related protein 1b (tyrp1b), but not tyrosinase (tyr). Last, Generally Applicable Gene set Enrichment (GAGE) analysis suggests autophagy pathway genes are upregulated together in crasher. Treatment with autophagy-inhibitor, Bafilomycin A1, significantly decreases melanophore number in crasher, suggesting ap3d1 promotes melanophore survival by limiting excessive autophagy. crasher is a valuable model to explore the regulation of melanogenesis gene expression and pigmentation disease.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes