Gene expression profiles of homogentisate-treated Fah-/- Hpd-/-mice using DNA microarrays.
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.
Tanaka
Yasuhiko
Y
Department of Pediatrics, Kumamoto University School of Medicine, Honjo 1-1-1, Kumamoto 860-8556, Japan.
Nakamura
Kimitoshi
K
Matsumoto
Shirou
S
Kimoto
Yoshiko
Y
Tanoue
Akito
A
Tsujimoto
Gozoh
G
Endo
Fumio
F
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D050560:Homogentisate 1,2-Dioxygenase / Q000378:metabolism; D006713:Homogentisic Acid / Q000494:pharmacology*; D006867:Hydrolases / Q000172:deficiency*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology; D051379:Mice; D008817:Mice, Mutant Strains; D019636:Neurodegenerative Diseases / Q000201:enzymology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010088:Oxidoreductases / Q000172:deficiency*; D000623:Porphobilinogen Synthase / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051906:Smad7 Protein / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D020176:Tyrosinemias / Q000201:enzymology; D015854:Up-Regulation / Q000187:drug effects
C488911:Hpd protein, mouse; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D014443:Tyrosine; D012313:RNA; D010088:Oxidoreductases; D050560:Homogentisate 1,2-Dioxygenase; D006867:Hydrolases; D020169:Caspases; C020156:fumarylacetoacetase; D000623:Porphobilinogen Synthase; D006713:Homogentisic Acid