A ZEBRAFISH MODEL FOR HEPATOERYTHROPOIETIC PORPHYRIA

Defects in the enzymes involved in the haem biosynthetic pathway can l ead to a group of human diseases known as the porphyrias. yquem (yqe(t p61)) is a zebrafish mutant with a photosensitive porphyria syndrome. Here we show that the porphyric phenotype is due to an inherited homoz ygous mutation in the gene encoding uroporphyrinogen decarboxylase (UR OD); a homozygous deficiency of this enzyme causes hepatoerythropoieti c porphyria (HEP) in humans. The zebrafish mutant represents the first genetically 'accurate' animal model of HEP, and should be useful for studying the pathogenesis of UROD deficiency and evaluating gene thera py vectors.. We rescued the mutant phenotype by transient and germline expression of the wild-type allele.