ArticlePloS one2018
A cre-inducible DUX4 transgenic mouse model for investigating facioscapulohumeral muscular dystrophy.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- FSHD muscle shows perturbation in fibroadipogenic progenitor cells, mitochondrial function and alternative splicing independently of inflammation.Human molecular genetics · 2024Pooled it
- Lipid nanoparticle delivery of antisense gapmers attenuates pathology in a mouse model of facioscapulohumeral muscular dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Transgenic mouse models for investigating human DUX4 expression during development and its roles in FSHD pathophysiology.Disease models & mechanisms · 2026Article
- Development of a DUX4-targeting antibody oligonucleotide conjugate as a therapy for FSHD.Nucleic acids research · 2026Article
- Article
- Matrix metalloproteinases are hallmark early biomarkers and therapeutic targets in FSHD.JCI insight · 2025Article
- AAV-shDUX4 provides short-term benefits but limited long-term efficacy in a DUX4 mouse model of FSHD.Molecular therapy. Methods & clinical development · 2025Article
- A systemically deliverable lipid-conjugated siRNA targeting DUX4 as an facioscapulohumeral muscular dystrophy therapeutic.Molecular therapy. Methods & clinical development · 2025Article
- DUX4 at 25: how it emerged from "junk DNA" to become the cause of facioscapulohumeral muscular dystrophy.Skeletal muscle · 2025Review
- Estrogen rescues muscle regeneration impaired by DUX4 in a humanized xenograft mouse model.Cell death & disease · 2025Article
- Muscular Dystrophies.Advances in experimental medicine and biology · 2025Review
- Molecular, Histological, and Functional Changes in Acta1-MCM;FLExDUX4/+ Mice.International journal of molecular sciences · 2024Article
- Oligonucleotide Therapies for Facioscapulohumeral Muscular Dystrophy: Current Preclinical Landscape.International journal of molecular sciences · 2024Review
- Systemic Pharmacotherapeutic Treatment of the ACTA1-MCM/FLExDUX4 Preclinical Mouse Model of FSHD.International journal of molecular sciences · 2024Article
- Engineered FSHD mutations results in D4Z4 heterochromatin disruption and feedforward DUX4 network activation.iScience · 2024Article
- Challenges and Considerations of Preclinical Development for iPSC-Based Myogenic Cell Therapy.Cells · 2024Review
- Voluntary wheel running improves molecular and functional deficits in a murine model of facioscapulohumeral muscular dystrophy.iScience · 2024Article
- Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism.Cell death & disease · 2023Article
- A Systemically Administered Unconjugated Antisense Oligonucleotide Targeting DUX4 Improves Muscular Injury and Motor Function in FSHD Model Mice.Biomedicines · 2023Article
- Molecular and Phenotypic Changes in FLExDUX4 Mice.Journal of personalized medicine · 2023Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The Double homeobox 4 (DUX4) gene is an important regulator of early human development and its aberrant expression is causal for facioscapulohumeral muscular dystrophy (FSHD). The DUX4-full length (DUX4-fl) mRNA splice isoform encodes a transcriptional activator; however, DUX4 and its unique DNA binding preferences are specific to old-world primates. Regardless, the somatic cytotoxicity caused by DUX4 expression is conserved when expressed in cells and animals ranging from fly to mouse. Thus, viable animal models based on DUX4-fl expression have been difficult to generate due in large part to overt developmental toxicity of low DUX4-fl expression from leaky transgenes. We have overcome this obstacle and here we report the generation and initial characterization of a line of conditional floxed DUX4-fl transgenic mice, FLExDUX4, that is viable and fertile. In the absence of cre, these mice express a very low level of DUX4-fl mRNA from the transgene, resulting in mild phenotypes. However, when crossed with appropriate cre-driver lines of mice, the double transgenic offspring readily express DUX4-fl mRNA, protein, and target genes with the spatiotemporal pattern of nuclear cre expression dictated by the chosen system. When cre is expressed from the ACTA1 skeletal muscle-specific promoter, the double transgenic animals exhibit a developmental myopathy. When crossed with tamoxifen-inducible cre lines, DUX4-mediated pathology can be induced in adult animals. Thus, the appearance and progression of pathology can be controlled to provide readily screenable phenotypes useful for assessing therapeutic approaches targeting DUX4-fl mRNA and protein. Overall, the FLExDUX4 line of mice is quite versatile and will allow new investigations into mechanisms of DUX4-mediated pathophysiology as well as much-needed pre-clinical testing of DUX4-targeted FSHD interventions in vivo.
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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.