| Popis: |
Zebrafish are an emerging model organism to study the syndromic albinism disorder, Hermansky-Pudlak syndrome (HPS), due to visible pigment development at 24 hours postfertilization, and conserved melanogenesis mechanisms. We describe crasher, a novel HPS type 10 (HPS10) zebrafish model, with a mutation in AP-3 complex subunit delta gene, 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. |
