Project description: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.

2023-04-04 | GSE225001 | GEO

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

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

| PRJNA845207 | ENA

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

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

| PRJNA678367 | ENA

Transcription profiling of mouse wild type, Fah and Fah, p21 ON and OFF NTBC animals

Project description:Fumarylacetoacetate hydrolase (Fah), the last enzyme of the tyrosine degradation pathway, is specifically expressed in hepatocytes in the liver. Loss of Fah leads to liver failure in mice within 6-8 weeks. This can be prevented by blocking tyrosine degradation upstream of Fah with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC). Here, we investigate the impact of p21 on global gene expression in Fah deficiency. Experiment Overall Design: Livers from adult wildtype, Fah or Fah, p21 knockout mice were analyzed either after continuous treatment (ON) with NTBC or after NTBC withdrawal for 14 days (OFF).

2008-06-11 | E-GEOD-11098 | biostudies-arrayexpress

Wildtype, Fah and Fah, p21 ON and OFF NTBC

2008-04-09 | GSE11098 | GEO

RNA-seq transcriptional profiling in the Fah-/- livers after transplantation and YC treatment

Project description:RNA-seq transcriptional profiling in the Fah-/- livers after transplantation and YC treatment

| PRJNA906443 | ENA

Human hepatocyte metaplasia in injured humanized mouse livers

Project description:The goal of this experiment was to test whether human hepatocytes could give rise to biliary-like progenitor cells in an in vivo context. Here Fah-/- Il2ry-/- Rag2-/-NOD mouse livers were humanized with human hepatocytes. Only hepatocytes engraft in the Fah-/- mouse at detectable levels in this model. Then animals were given chronic liver injury with 0.1% ddc. After injury we measured human-specific transcripts to determine whether the phenotype of the human cells had changed. Specifically, we evaluated the relative levels of human biliary duct markers such as Spp1, Sox9, Krt7, etc. and hepatocyte markers such as Alb, Ttr, Fah, etc.

2014-09-01 | GSE58679 | GEO

Human hepatocyte metaplasia in injured humanized mouse livers

2014-09-01 | E-GEOD-58679 | biostudies-arrayexpress