Gene expression profiles of homogentisate-treated Fah-/- Hpd-/-mice using DNA microarrays.

Abstract

Hereditary tyrosinemia I (HT I) is a genetic disorder of tyrosine metabolism caused by abnormalities of fumarylacetoacetate hydrolase. Disturbances in tyrosine metabolism lead to increased levels of succinylacetone and succinylacetoacetate. However, the mechanisms causing liver failure, cirrhosis, renal tubular dysfunction, and hepatocarcinoma are still unknown. Alterations in gene expression found in the livers of patients with HT I are responsible for the pathogenesis of this disease, for example acute liver failure. Therefore, gene expression analysis allows us to better understand its pathogenesis. We analyzed gene expressions in tyrosinemia type I model mice with liver failure using microarrays. The results were confirmed by quantitative PCR to evaluate the pathogenesis of tyrosinemia type I. We found that numerous genes, including amino acid metabolism and apoptosis related genes, were up- or down-regulated at the onset of liver failure. These findings are useful in understanding the pathogenesis of hereditary tyrosinemia.

• Authors: Yasuhiko Tanaka, Kimitoshi Nakamura, Shirou Matsumoto, Yoshiko Kimoto, Akito Tanoue, Gozoh Tsujimoto, Fumio Endo
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 89 Issue 3 Pg. 203-9 (Nov 2006) ISSN: 1096-7192 [Print] United States
• PMID: 16899383 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hpd protein, mouse
• Smad7 Protein
• Smad7 protein, mouse
• Tyrosine
• RNA
• Oxidoreductases
• Homogentisate 1,2-Dioxygenase
• Hydrolases
• Caspases
• fumarylacetoacetase
• Porphobilinogen Synthase
• Homogentisic Acid

Topics

• Animals
• Apoptosis (drug effects)
• Caspases (metabolism)
• Down-Regulation (drug effects)
• Female
• Gene Expression Profiling
• Homogentisate 1,2-Dioxygenase (metabolism)
• Homogentisic Acid (pharmacology)
• Hydrolases (deficiency)
• Liver (cytology, drug effects, physiopathology)
• Mice
• Mice, Mutant Strains
• Neurodegenerative Diseases (enzymology)
• Oligonucleotide Array Sequence Analysis (methods)
• Oxidoreductases (deficiency)
• Porphobilinogen Synthase (metabolism)
• RNA (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Smad7 Protein (metabolism)
• Tyrosine (metabolism)
• Tyrosinemias (enzymology)
• Up-Regulation (drug effects)