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

Curr Biol. 2000 Aug 24;10(16):1001-4. doi: 10.1016/s0960-9822(00)00653-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

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


  • Protoporphyrins
  • protoporphyrin IX
  • Ferrochelatase