Zebrafish dracula encodes ferrochelatase and its mutation provides a modelfor erythropoietic protoporphyria

Exposure to light precipitates the symptoms of several genetic disorders th at 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 t he first days of development. In a previous large-scale genetic screen we i solated a mutation, dracula (drc), which manifested as a light-dependent ly sis of red blood cells [1]. We report here that protoporphyrin IX accumulat es in the mutant embryos, suggesting a deficiency in the activity of ferroc helatase, the terminal enzyme in the pathway for heme biosynthesis. We find that homozygous drc(m248) mutant embryos have a G-->T transversion at a sp lice donor site in the ferrochelatase gene, creating a premature stop codon . The mutant phenotype, which shows light-dependent hemolysis and liver dis ease, is similar to that seen in humans with erythropoietic protoporphyria, a disorder of ferrochelatase.