The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Tyrosinaemia type I and apoptosis of hepatocytes and renal tubular cells.

Hereditary tyrosinaemia type I (HT 1) (McKusick 276700) is caused by a deficiency of fumarylacetoacetate hydrolase ( FAH) activity, the last enzyme in the tyrosine catabolic pathway. Homozygous disruption of the gene encoding FAH in mice (Fah) causes neonatal lethality (i.e. lethal Albino deletion c14CoS mice), which limits the use of this animal as a model for HT I. We developed a new mouse model that carries two genetic defects, Fah and 4-hydroxyphenylpyruvate dioxygenase (Hpd). The double mutant Fah -/- Hpd -/- mice grew normally without evidence of liver and renal disease, showing a phenotype similar to Hpd -/- mice. Complete blockage of the tyrosine catabolic pathway at the, step of HPD prevents development of clinical phenotypes. Administration of homogentisate resulted in rapid apoptosis of hepatocytes and renal tubular epithelial cells, a central feature of visceral injury in patients with HT I. Simultaneously, renal tubular function was impaired, resulting in Fanconi syndrome. Apoptosis of hepatocyte and renal tubular cells is prevented by the caspase inhibitors YVAD or DEVD. However, these inhibitors do not prevent the release of cytochrome c or the development of renal tubular dysfunction. Apoptosis of hepatocytes and of renal tubular epithelial cells are characteristic features of this disease and the apoptotic signal in this disease seems to be initiated by fumarylacetoacetate.[1]


  1. Tyrosinaemia type I and apoptosis of hepatocytes and renal tubular cells. Endo, F., Sun, M.S. J. Inherit. Metab. Dis. (2002) [Pubmed]
WikiGenes - Universities