ArticleDisease models & mechanisms2016
Mice with missense and nonsense NF1 mutations display divergent phenotypes compared with human neurofibromatosis type I.
Article in Disease models & mechanisms, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 30 citations in OpenAlex.
- Current states in understanding oligodendroglia-mediated neurological issues in neurofibromatosis type 1 (NF1).Acta neuropathologica communications · 2025Review
- Repair of MutatedCancers · 2025Article
- Cognition and behavior in neurofibromatosis type 1: report and perspective from the Cognition and Behavior in NF1 (CABIN) Task Force.Genes & development · 2025Article
- The evolving landscape of NF gene therapy: Hurdles and opportunities.Molecular therapy. Nucleic acids · 2025Review
- Human single cell RNA-sequencing reveals a targetable CD8Nature communications · 2024Article
- Nf1 mutation disrupts activity-dependent oligodendroglial plasticity and motor learning in mice.Nature neuroscience · 2024Article
- Developing AAV-delivered nonsense suppressor tRNAs for neurological disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Cost-effective Whole Exome Sequencing discovers pathogenic variant causing Neurofibromatosis type 1 in a family from Jammu and Kashmir, India.Scientific reports · 2023Article
- Recoding of Nonsense Mutation as a Pharmacological Strategy.Biomedicines · 2023Review
- Targeted pseudouridylation: An approach for suppressing nonsense mutations in disease genes.Molecular cell · 2023Article
- Destabilizing NF1 variants act in a dominant negative manner through neurofibromin dimerization.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Functional restoration of mouse Nf1 nonsense alleles in differentiated cultured neurons.Journal of human genetics · 2022Article
- Targeted exon skipping ofMolecular therapy. Nucleic acids · 2022Article
- Developmental, neurochemical, and behavioral analyses of ErbB4 Cyt-1 knockout mice.Journal of neurochemistry · 2022Article
- Neuronal hyperexcitability drives central and peripheral nervous system tumor progression in models of neurofibromatosis-1.Nature communications · 2022Article
- Restoration of Normal NF1 Function with Antisense Morpholino Treatment of Recurrent Pathogenic Patient-Specific Variant c.1466A>G; p.Y489C.Journal of personalized medicine · 2021Article
- Shared developmental gait disruptions across two mouse models of neurodevelopmental disorders.Journal of neurodevelopmental disorders · 2021Article
- Clinical manifestation and genetic findings in three boys with low molecular Weight Proteinuria - three case reports for exploring Dent Disease and Fanconi syndrome.BMC nephrology · 2021Article
- Targeting Nonsense: Optimization of 1,2,4-Oxadiazole TRIDs to Rescue CFTR Expression and Functionality in Cystic Fibrosis Cell Model Systems.International journal of molecular sciences · 2020Article
- Mutation-Directed Therapeutics for Neurofibromatosis Type I.Molecular therapy. Nucleic acids · 2020Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized by the occurrence of nerve sheath tumors and considerable clinical heterogeneity. Some translational studies have been limited by the lack of animal models available for assessing patient-specific mutations. In order to test therapeutic approaches that might restore function to the mutated gene or gene product, we developed mice harboring NF1 patient-specific mutations including a nonsense mutation (c.2041C>T; p.Arg681*) and a missense mutation (c.2542G>C; p.Gly848Arg). The latter is associated with the development of multiple plexiform neurofibromas along spinal nerve roots. We demonstrate that the human nonsense NF1(Arg681*) and missense NF1(Gly848Arg) mutations have different effects on neurofibromin expression in the mouse and each recapitulates unique aspects of the NF1 phenotype, depending upon the genetic context when assessed in the homozygous state or when paired with a conditional knockout allele. Whereas the missense Nf1(Gly848Arg) mutation fails to produce an overt phenotype in the mouse, animals homozygous for the nonsense Nf1(Arg681*) mutation are not viable. Mice with one Nf1(Arg681*) allele in combination with a conditional floxed Nf1 allele and the DhhCre transgene (Nf1(4F/Arg681*); DhhCre) display disorganized nonmyelinating axons and neurofibromas along the spinal column, which leads to compression of the spinal cord and paralysis. This model will be valuable for preclinical testing of novel nonsense suppression therapies using drugs to target in-frame point mutations that create premature termination codons in individuals with NF1.
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