ArticleThe Journal of clinical investigation2012
Mutant TDP-43 in motor neurons promotes the onset and progression of ALS in rats.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed.
- Caspase-4 transgenic mice exhibit cytoplasmic TDP-43 accumulation and age-dependent neuropathology.Nature communications · 2026Article
- Co-localization of tau and TDP-43 after extracellular vesicle delivery to cells.The FEBS journal · 2026Article
- Astrocytes expressing mutant hnRNPA1 induce non-cell-autonomous motor neuron death.Brain research bulletin · 2025Article
- A Slower-Progressing TDP-43 rNLS8 Mouse Model for ALS: Implications for Preclinical and Mechanistic Studies.Neuromolecular medicine · 2025Article
- Bidirectional Interplay Between Microglia and Mast Cells.International journal of molecular sciences · 2025Review
- Ribosome-associated pathological TDP-43 alters the expression of multiple mRNAs in the monkey brain.Zoological research · 2025Article
- ALS-linked mutant TDP-43 in oligodendrocytes induces oligodendrocyte damage and exacerbates motor dysfunction in mice.Acta neuropathologica communications · 2024Article
- Endoplasmic reticulum unfolded protein response transcriptional targets of XBP-1s mediate rescue from tauopathy.Communications biology · 2024Article
- Genetically modified non-human primate models for research on neurodegenerative diseases.Zoological research · 2024Review
- A technique for repeated blood and cerebrospinal fluid sampling from individual rats over time without the need for repeated anesthesia.Scientific reports · 2024Article
- Loss of TDP-43 mediates severe neurotoxicity by suppressing PJA1 gene transcription in the monkey brain.Cellular and molecular life sciences : CMLS · 2024Article
- Potential contribution of spinal interneurons to the etiopathogenesis of amyotrophic lateral sclerosis.Frontiers in neuroscience · 2024Review
- Increase in hnRNPA1 Expression Suffices to Kill Motor Neurons in Transgenic Rats.International journal of molecular sciences · 2023Article
- Pathological insights from amyotrophic lateral sclerosis animal models: comparisons, limitations, and challenges.Translational neurodegeneration · 2023Review
- CDNF rescues motor neurons in models of amyotrophic lateral sclerosis by targeting endoplasmic reticulum stress.Brain : a journal of neurology · 2023Article
- APOE2 Exacerbates TDP-43 Related Toxicity in the Absence of Alzheimer Pathology.Annals of neurology · 2023Article
- Detergent-insoluble PFN1 inoculation expedites disease onset and progression in PFN1 transgenic rats.Frontiers in neuroscience · 2023Article
- New pathogenic insights from large animal models of neurodegenerative diseases.Protein & cell · 2022Review
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12 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron degeneration, which ultimately leads to paralysis and death. Mutation of TAR DNA binding protein 43 (TDP-43) has been linked to the development of an inherited form of ALS. Existing TDP-43 transgenic animals develop a limited loss of motor neurons and therefore do not faithfully reproduce the core phenotype of ALS. Here, we report the creation of multiple lines of transgenic rats in which expression of ALS-associated mutant human TDP-43 is restricted to either motor neurons or other types of neurons and skeletal muscle and can be switched on and off. All of these rats developed progressive paralysis reminiscent of ALS when the transgene was switched on. Rats expressing mutant TDP-43 in motor neurons alone lost more spinal motor neurons than rats expressing the disease gene in varying neurons and muscle cells, although these rats all developed remarkable denervation atrophy of skeletal muscles. Intriguingly, progression of the disease was halted after transgene expression was switched off; in rats with limited loss of motor neurons, we observed a dramatic recovery of motor function, but in rats with profound loss of motor neurons, we only observed a moderate recovery of motor function. Our finding suggests that mutant TDP-43 in motor neurons is sufficient to promote the onset and progression of ALS and that motor neuron degeneration is partially reversible, at least in mutant TDP-43 transgenic rats.
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