title: Zebrafish dracula encodes ferrochelatase and its mutation provides a model for erythropoietic protoporphyria.
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.
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital East, Charlestown 02129, USA.
authors.forename: S
authors.initials: S
authors.lastname: Childs
authors.forename: B M
authors.initials: BM
authors.lastname: Weinstein
authors.forename: M A
authors.initials: MA
authors.lastname: Mohideen
authors.forename: S
authors.initials: S
authors.lastname: Donohue
authors.forename: H
authors.initials: H
authors.lastname: Bonkovsky
authors.forename: M C
authors.initials: MC
authors.lastname: Fishman
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005294:Ferrochelatase / Q000235:genetics* / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D008027:Light; D008107:Liver Diseases / Q000503:physiopathology; D009154:Mutation; D017121:Porphyria, Hepatoerythropoietic; D046351:Protoporphyria, Erythropoietic; D011524:Protoporphyrins / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000378:metabolism
chemical_list: D011524:Protoporphyrins; C028025:protoporphyrin IX; D005294:Ferrochelatase