ArticleBrain : a journal of neurology2017
Humanized mutant FUS drives progressive motor neuron degeneration without aggregation in 'FUSDelta14' knockin mice.
Article in Brain : a journal of neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 122 citations in OpenAlex.
- Autoimmune processes and production of catalytically active antibodies-abzymes in prone to amyotrophic lateral sclerosis FUS(1-359) mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- FUS controls muscle differentiation through phase separation-mediated recruitment of the transcription factors MEF2 and ETV5.The EMBO journal · 2026Article
- M6A-dependent RNA condensation underlies FUS autoregulation and can be harnessed for ALS therapy development.Science advances · 2025Article
- RNA-binding proteins in ALS and FTD: from pathogenic mechanisms to therapeutic insights.Molecular neurodegeneration · 2025Review
- Single-cell RNA-sequencing reveals early mitochondrial dysfunction unique to motor neurons shared across FUS- and TARDBP-ALS.Nature communications · 2025Article
- Aberrant protein aggregation in amyotrophic lateral sclerosis.Journal of neurology · 2024Review
- Frontotemporal dementia-like disease progression elicited by seeded aggregation and spread of FUS.Molecular neurodegeneration · 2024Article
- hnRNP A1 dysfunction alters RNA splicing and drives neurodegeneration in multiple sclerosis (MS).Nature communications · 2024Article
- hnRNPs: roles in neurodevelopment and implication for brain disorders.Frontiers in molecular neuroscience · 2024Review
- Mimicking hypomethylation of FUS requires liquid-liquid phase separation to induce synaptic dysfunctions.Acta neuropathologica communications · 2023Article
- Mutation in the FUS nuclear localisation signal domain causes neurodevelopmental and systemic metabolic alterations.Disease models & mechanisms · 2023Article
- Nutritional and metabolic factors in amyotrophic lateral sclerosis.Nature reviews. Neurology · 2023Review
- Cytoplasmic aggregation of mutant FUS causes multistep RNA splicing perturbations in the course of motor neuron pathology.Nucleic acids research · 2023Article
- Opinion: more mouse models and more translation needed for ALS.Molecular neurodegeneration · 2023Review
- Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation.Nature reviews. Drug discovery · 2023Review
- Small junction, big problems: Neuromuscular junction pathology in mouse models of amyotrophic lateral sclerosis (ALS).Journal of anatomy · 2022Review
- Modelling amyotrophic lateral sclerosis in rodents.Nature reviews. Neuroscience · 2022Review
- Neuromuscular Junction Dysfunction in Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2022Review
- Screening and validation of genome-edited animals.Laboratory animals · 2022Article
- Alternative Splicing in Human Biology and Disease.Methods in molecular biology (Clifton, N.J.) · 2022Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 6 institutions in 3 countries.
Funding
Abstract
Mutations in FUS are causative for amyotrophic lateral sclerosis with a dominant mode of inheritance. In trying to model FUS-amyotrophic lateral sclerosis (ALS) in mouse it is clear that FUS is dosage-sensitive and effects arise from overexpression per se in transgenic strains. Novel models are required that maintain physiological levels of FUS expression and that recapitulate the human disease-with progressive loss of motor neurons in heterozygous animals. Here, we describe a new humanized FUS-ALS mouse with a frameshift mutation, which fulfils both criteria: the FUS Delta14 mouse. Heterozygous animals express mutant humanized FUS protein at physiological levels and have adult onset progressive motor neuron loss and denervation of neuromuscular junctions. Additionally, we generated a novel antibody to the unique human frameshift peptide epitope, allowing specific identification of mutant FUS only. Using our new FUSDelta14 ALS mouse-antibody system we show that neurodegeneration occurs in the absence of FUS protein aggregation. FUS mislocalization increases as disease progresses, and mutant FUS accumulates at the rough endoplasmic reticulum. Further, transcriptomic analyses show progressive changes in ribosomal protein levels and mitochondrial function as early disease stages are initiated. Thus, our new physiological mouse model has provided novel insight into the early pathogenesis of FUS-ALS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.