ArticleMolecular neurodegeneration2015
Cytoplasmic mislocalization of RNA splicing factors and aberrant neuronal gene splicing in TDP-43 transgenic pig brain.
Article in Molecular neurodegeneration, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 61 citations in OpenAlex.
- UA-30 ameliorates motor deficits through RalA-mediated mitophagy in ALS mice.The Journal of clinical investigation · 2026Article
- Caspase-4 transgenic mice exhibit cytoplasmic TDP-43 accumulation and age-dependent neuropathology.Nature communications · 2026Article
- Calretinin and Parvalbumin Trapping of TDP43 and XRCC1 Instructs Neocortical Interneuron Death in Neonatal Hypoxic-Ischemic Encephalopathy.Biomolecules · 2026Article
- Alleviation of mutant TDP-43-mediated neuropathology by inducible stem cells in monkeys.International journal of biological sciences · 2026Article
- RNA/DNA-binding protein TDP43 regulates DNA mismatch repair genes with implications for genome stability.Nucleic acids research · 2025Article
- Article
- Research advances in dysphagia animal models.Animal models and experimental medicine · 2025Review
- RNA/DNA Binding Protein TDP43 Regulates DNA Mismatch Repair Genes with Implications for Genome Stability.bioRxiv : the preprint server for biology · 2025Article
- Gene therapy breakthroughs in ALS: a beacon of hope for 20% of ALS patients.Translational neurodegeneration · 2025Review
- Ribosome-associated pathological TDP-43 alters the expression of multiple mRNAs in the monkey brain.Zoological research · 2025Article
- SARS-CoV-2 Rapidly Infects Peripheral Sensory and Autonomic Neurons, Contributing to Central Nervous System Neuroinvasion before Viremia.International journal of molecular sciences · 2024Article
- Genetically modified non-human primate models for research on neurodegenerative diseases.Zoological research · 2024Review
- Drug Screening and Validation Targeting TDP-43 Proteinopathy for Amyotrophic Lateral Sclerosis.Aging and disease · 2024Review
- Loss of TDP-43 mediates severe neurotoxicity by suppressing PJA1 gene transcription in the monkey brain.Cellular and molecular life sciences : CMLS · 2024Article
- Role of RNA binding proteins of theRNA biology · 2024Review
- Three-dimensional surface motion capture of multiple freely moving pigs using MAMMAL.Nature communications · 2023Article
- Pathological insights from amyotrophic lateral sclerosis animal models: comparisons, limitations, and challenges.Translational neurodegeneration · 2023Review
- LAFITE Reveals the Complexity of Transcript Isoforms in Subcellular Fractions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Prematurely terminated intron-retaining mRNAs invade axons in SFPQ null-driven neurodegeneration and are a hallmark of ALS.Nature communications · 2022Article
- Double knock-in pig models with elements of binary Tet-On and phiC31 integrase systems for controllable and switchable gene expression.Science China. Life sciences · 2022Article
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundTAR DNA-binding protein 43 (TDP-43) is a nuclear protein, but it is redistributed in the neuronal cytoplasm in both amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Because small transgenic animal models often lack cytoplasmic TDP-43, how the cytoplasmic accumulation of TDP-43 contributes to these diseases remains unclear. The current study is aimed at studying the mechanism of cytoplasmic pathology of TDP-43.
resultsWe established transgenic pigs expressing mutant TDP-43 (M337V). This pig model shows severe phenotypes and early death. We found that transgenic TDP-43 is also distributed in the cytoplasm of neuronal cells in the spinal cord and brain. Transgenic TDP-43 interacts with PSF, an RNA splicing factor that associates with NeuN to regulate neuronal RNA splicing. The interaction of TDP-43, PSF and NeuN causes PSF and NeuN mislocalize into the neuronal cytoplasm in transgenic pigs. Consistently, abnormal PSF-related neuronal RNA splicing is seen in TDP-43 transgenic pigs. The cytoplasmic localization of PSF and NeuN as well as abnormal PSF-related neuronal RNA splicing was also found in ALS patient brains.
conclusionOur findings from a large mammalian model suggest that cytoplasmic mutant TDP-43 could reduce the nuclear function of RNA splicing factors, contributing to neuropathology.
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