PUBLICATION

Zebrafish dracula encodes ferrochelatase and its mutation provides a model for erythropoietic protoporphyria

Authors
Childs, S., Weinstein, B.M., Mohideen, M.A.P.K., Donohue, S., Bonkovsky, H., and Fishman, M.C.
ID
ZDB-PUB-000927-2
Date
2000
Source
Current biology : CB   10(16): 1001-1004 (Journal)
Registered Authors
Bonkovsky, Josh, Childs, Sarah J., Fishman, Mark C., Mohideen, Manzoor Pallithotangal, Weinstein, Brant M.
Keywords
none
MeSH Terms
  • Animals
  • Disease Models, Animal*
  • Ferrochelatase/genetics*
  • Ferrochelatase/metabolism
  • Hemolysis
  • Humans
  • Light
  • Liver Diseases/physiopathology
  • Mutation*
  • Porphyria, Hepatoerythropoietic*
  • Protoporphyria, Erythropoietic
  • Protoporphyrins/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/metabolism
PubMed
10985389 Full text @ Curr. Biol.
Abstract
Exposure to light precipitates the symptoms of several genetic disorders that affect both skin and internal organs. It is presumed that damage to non-cutaneous organs is initiated indirectly by light, but this is difficult to study in mammals. Zebrafish have an essentially transparent periderm for the first days of development. In a previous large-scale genetic screen we isolated a mutation, dracula (drc), which manifested as a light-dependent lysis of red blood cells [1].We report here that protoporphyrin IX accumulates in the mutant embryos, suggesting a deficiency in the activity of ferrochelatase, the terminal enzyme in the pathway for heme biosynthesis. We find that homozygous drc(m248) mutant embryos have a G-->T transversion at a splice donor site in the ferrochelatase gene, creating a premature stop codon. The mutant phenotype, which shows light-dependent hemolysis and liver disease, is similar to that seen in humans with erythropoietic protoporphyria, a disorder of ferrochelatase.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping