Nature Genetics volume 10 august 1995 Pharmacological correction of neonatal lethal hepatic dysfunction in a murine model of hereditary tyrosinaemia type I

Markus Grompe, Sven Lindstedt, Muhsen Al-Dhalimy, Nancy G. Kennaway, John Papaconstantinou, Carlos A. Torres-Ramos, Ching Nan Ou, Milton Finegold

Research output: Contribution to journalArticle

224 Citations (Scopus)

Abstract

Hereditary tyrosinaemia type I, a severe autosomal recessive metabolic disease, affects the liver and kidneys and is caused by deficiency of fumarylacetoacetate hydrolase (FAH). Mice homozygous for a FAH gene disruption have a neonatal lethal phenotype caused by liver dysfunction and do not represent an adequate model of the human disease. Here we demonstrate that treatment of affected animals with 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3-cyclohexanedione abolished neonatal lethality, corrected liver function and partially normalized the altered expression pattern of hepatic mRNAs. The prolonged lifespan of affected animals resulted in a phenotype analogous to human tyrosinaemia type I including hepatocellular carcinoma. The adult FAH-/- mouse will serve as useful model for studies of the pathophysiology and treatment of hereditary tyrosinaemia type I as well as hepatic cancer.

Original languageEnglish (US)
Pages (from-to)453-460
Number of pages8
JournalNature Genetics
Volume10
Issue number4
StatePublished - Aug 1995

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Tyrosinemias
Pharmacology
Liver
Phenotype
Metabolic Diseases
Liver Neoplasms
Liver Diseases
Hepatocellular Carcinoma
Kidney
Messenger RNA
Genes
fumarylacetoacetase

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Nature Genetics volume 10 august 1995 Pharmacological correction of neonatal lethal hepatic dysfunction in a murine model of hereditary tyrosinaemia type I. / Grompe, Markus; Lindstedt, Sven; Al-Dhalimy, Muhsen; Kennaway, Nancy G.; Papaconstantinou, John; Torres-Ramos, Carlos A.; Ou, Ching Nan; Finegold, Milton.

In: Nature Genetics, Vol. 10, No. 4, 08.1995, p. 453-460.

Research output: Contribution to journalArticle

Grompe, M, Lindstedt, S, Al-Dhalimy, M, Kennaway, NG, Papaconstantinou, J, Torres-Ramos, CA, Ou, CN & Finegold, M 1995, 'Nature Genetics volume 10 august 1995 Pharmacological correction of neonatal lethal hepatic dysfunction in a murine model of hereditary tyrosinaemia type I', Nature Genetics, vol. 10, no. 4, pp. 453-460.
Grompe, Markus ; Lindstedt, Sven ; Al-Dhalimy, Muhsen ; Kennaway, Nancy G. ; Papaconstantinou, John ; Torres-Ramos, Carlos A. ; Ou, Ching Nan ; Finegold, Milton. / Nature Genetics volume 10 august 1995 Pharmacological correction of neonatal lethal hepatic dysfunction in a murine model of hereditary tyrosinaemia type I. In: Nature Genetics. 1995 ; Vol. 10, No. 4. pp. 453-460.
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