A mutation in the silver gene leads to defects in melanosome biogenesis and alterations in the visual system in the zebrafish mutant fading vision

Schonthaler, H.B., Lampert, J.M., von Lintig, J., Schwarz, H., Geisler, R., and Neuhauss, S.C.
Developmental Biology   284(2): 421-436 (Journal)
Registered Authors
Geisler, Robert, Lampert, Johanna, Neuhauss, Stephan
Danio rerio, Melanosome, Retinal pigment epithelium, Visual cycle, Photoreceptor, Silver, Pmel17
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromosomes
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Genetic Linkage
  • Genetic Markers
  • Genome
  • Homozygote
  • Melanocytes/ultrastructure
  • Melanosomes/physiology*
  • Melanosomes/ultrastructure
  • Molecular Sequence Data
  • Photoreceptor Cells, Vertebrate/ultrastructure
  • Pigment Epithelium of Eye/ultrastructure
  • Point Mutation*
  • Polymorphism, Genetic
  • Protein Sorting Signals
  • Protein Structure, Tertiary
  • Radiation Hybrid Mapping
  • Sequence Analysis, DNA
  • Sequence Analysis, Protein
  • Sequence Homology, Amino Acid
  • Vision, Ocular/genetics
  • Vision, Ocular/physiology*
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/physiology
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/genetics*
16024012 Full text @ Dev. Biol.
Forward genetic screens have been instrumental in defining molecular components of visual function. The zebrafish mutant fading vision (fdv) has been identified in such a screen due to defects in vision accompanied by hypopigmentation in the retinal pigment epithelium (RPE) and body melanocytes. The RPE forms the outer most layer of the retina, and its function is essential for vision. In fdv mutant larvae, the outer segments of photoreceptors are strongly reduced in length or absent due to defects in RPE cells. Ultrastructural analysis of RPE cells reveals dramatic cellular changes such as an absence of microvilli and vesicular inclusions. The retinoid profile is altered as judged by biochemical analysis, arguing for a partial block in visual pigment regeneration. Surprisingly, homozygous fdv vision mutants survive to adulthood and show, despite a persistence of the hypopigmentation, a partial recovery of retinal morphology. By positional cloning and subsequent morpholino knock-down, we identified a mutation in the silver gene as the molecular defect underlying the fdv phenotype. The Silver protein is required for intralumenal fibril formation in melanosomes by amylogenic cleavage. Our data reveal an unexpected link between melanosome biogenesis and the visual system, undetectable in cell culture.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes