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.
Citation
Childs, S., Weinstein, B.M., Mohideen, M.A.P.K., Donohue, S., Bonkovsky, H., and Fishman, M.C. (2000) Zebrafish dracula encodes ferrochelatase and its mutation provides a model for erythropoietic protoporphyria. Current biology : CB. 10(16):1001-1004.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping