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Gene expression profiling of Fah- and Hgd-deficient mouse livers upon short-term nitisinone discontinuation

ABSTRACT: Hereditary tyrosinemia type 1 (HT1) is a severe genetic disorder that affects the liver due to a defective fumarylacetoacetate hydrolase (Fah) enzyme in hepatocytes. The drug nitisinone (NTBC) has offered a life-saving treatment for HT1 patients by inhibiting the upstream enzyme 4-hydroxyphenylpyruvate dioxygenase (HPD). We used microarray analyses to to identify changes in molecular pathways associated to the development and progression of the liver pathogenesis of HT1 that remain uncorrected under NTBC therapy by using gene expression profiling of Fah-deficient mouse livers subjected to continuous NTBC therapy and after seven days of NTBC therapy discontinuation. As a control of a TIMD without hepatic manifestation, we used the Hgd-deficient mouse model of AKU, also under continuous NTBC treatment and after seven days of NTBC therapy discontinuation. Consequently, we identified a set of 25 genes that discriminates HT1 livers from AKU livers, even under continuous NTBC therapy, as such representing remnants of an HT1-driven residual uncorrected liver disease phenotype.

ORGANISM(S): Mus musculus

PROVIDER: GSE225001 | GEO | 2023/04/04

REPOSITORIES: GEO

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Gene expression profiling of Fah-deficient mouse livers upon short-term nitisinone discontinuation

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