Wang H, Long Q, Marty S D, Sassa S, Lin S
Institute of Molecular Medicine and Genetics & Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912, USA.
Nat Genet. 1998 Nov;20(3):239-43. doi: 10.1038/3041.
Defects in the enzymes involved in the haem biosynthetic pathway can lead to a group of human diseases known as the porphyrias. yquem (yqe(tp61)) is a zebrafish mutant with a photosensitive porphyria syndrome. Here we show that the porphyric phenotype is due to an inherited homozygous mutation in the gene encoding uroporphyrinogen decarboxylase (UROD); a homozygous deficiency of this enzyme causes hepatoerythropoietic 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 therapy vectors. We rescued the mutant phenotype by transient and germline expression of the wild-type allele.
血红素生物合成途径中相关酶的缺陷可导致一类被称为卟啉症的人类疾病。伊甘（yqe(tp61)）是一种患有光敏性卟啉症综合征的斑马鱼突变体。我们在此表明，卟啉症表型是由于编码尿卟啉原脱羧酶（UROD）的基因中存在遗传性纯合突变；这种酶的纯合缺陷在人类中会导致肝红细胞生成性卟啉症（HEP）。该斑马鱼突变体代表了首个基因“精确”的HEP动物模型，应有助于研究UROD缺陷的发病机制以及评估基因治疗载体。我们通过野生型等位基因的瞬时和种系表达挽救了突变体表型。
