ArticleProceedings of the National Academy of Sciences of the United States of America2001
Point mutations in the murine fumarylacetoacetate hydrolase gene: Animal models for the human genetic disorder hereditary tyrosinemia type 1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed.
- Non-viral delivery of genome-editing tools for treatment of genetic disorders.Acta pharmaceutica Sinica. B · 2026Review
- Self-delivering, chemically modified CRISPR RNAs for AAV co-delivery and genome editing in vivo.Nucleic acids research · 2024Article
- mRNA-based therapy proves superior to the standard of care for treating hereditary tyrosinemia 1 in a mouse model.Molecular therapy. Methods & clinical development · 2022Article
- Adenine Base EditingGEN biotechnology · 2022Article
- Application of prime editing to the correction of mutations and phenotypes in adult mice with liver and eye diseases.Nature biomedical engineering · 2022Article
- Self-inactivating, all-in-one AAV vectors for precision Cas9 genome editing via homology-directed repair in vivo.Nature communications · 2021Article
- Induced Liver Regeneration Enhances CRISPR/Cas9-Mediated Gene Repair in Tyrosinemia Type 1.Human gene therapy · 2021Article
- Progress and challenges in CRISPR-mediated therapeutic genome editing for monogenic diseases.Journal of biomedical research · 2020Article
- A Compensatory U1snRNA Partially Rescues FAH Splicing and Protein Expression in a Splicing-Defective Mouse Model of Tyrosinemia Type I.International journal of molecular sciences · 2020Article
- Somatic Liver Knockout (SLiK): A Quick and Efficient Way to Generate Liver-Specific Knockout Mice Using Multiplex CRISPR/Cas9 Gene Editing.Current protocols in molecular biology · 2020Article
- Genome editing technologies to treat rare liver diseases.Translational gastroenterology and hepatology · 2020Review
- CRISPR/Cas9-related technologies in liver diseases: from feasibility to future diversity.International journal of biological sciences · 2020Review
- Adenine base editing in an adult mouse model of tyrosinaemia.Nature biomedical engineering · 2020Article
- Tissue-specific FAH deficiency alters sleep-wake patterns and results in chronic tyrosinemia in mice.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Gene and Base Editing as a Therapeutic Option for Cystic Fibrosis-Learning from Other Diseases.Genes · 2019Review
- Article
- Cas9-mediated allelic exchange repairs compound heterozygous recessive mutations in mice.Nature biotechnology · 2018Article
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- Non-viral delivery systems for CRISPR/Cas9-based genome editing: Challenges and opportunities.Biomaterials · 2018Review
- Genome editing for the reproduction and remedy of human diseases in mice.Journal of human genetics · 2018Review
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9 authors.
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Abstract
Hereditary tyrosinemia type 1 (HT1) is a severe autosomal recessive metabolic disease associated with point mutations in the human fumarylacetoacetate hydrolase (FAH) gene that disrupt tyrosine catabolism. An acute form of HT1 results in death during the first months of life because of hepatic failure, whereas a chronic form leads to gradual development of liver disease often accompanied by renal dysfunction, childhood rickets, neurological crisis, and hepatocellular carcinoma. Mice homozygous for certain chromosome 7 deletions of the albino Tyr; c locus that also include Fah die perinatally as a result of liver dysfunction and exhibit a complex syndrome characterized by structural abnormalities and alterations in gene expression in the liver and kidney. Here we report that two independent, postnatally lethal mutations induced by N-ethyl-N-nitrosourea and mapped near Tyr are alleles of Fah. The Fah(6287SB) allele is a missense mutation in exon 6, and Fah(5961SB) is a splice mutation causing loss of exon 7, a subsequent frameshift in the resulting mRNA, and a severe reduction of Fah mRNA levels. Increased levels of the diagnostic metabolite succinylacetone in the urine of the Fah(6287SB) and Fah(5961SB) mutants indicate that these mutations cause a decrease in Fah enzymatic activity. Thus, the neonatal phenotype present in both mutants is due to a deficiency in Fah caused by a point mutation, and we propose Fah(5961SB) and Fah(6287SB) as mouse models for acute and chronic forms of human HT1, respectively.
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