ArticleThe Journal of biological chemistry2014
Mitochondrial dysfunction and decrease in body weight of a transgenic knock-in mouse model for TDP-43.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 139 citations in OpenAlex.
- TDP-43 oxidation and PP1 crosstalk at RNA granule-mitochondria contact sites.Nature communications · 2026Article
- Selective Silencing of TDP-43 P. G376D Mutation Reverses Key Amyotrophic Lateral Sclerosis-Related Cellular Deficits.Biomolecules · 2026Article
- C9orf72-ALS mutation drives basal mitophagy impairments in iNeurons.Frontiers in cellular neuroscience · 2026Article
- The mechanisms underlying TDP-43-associated neurodegeneration in Alzheimer's disease and related dementias.Molecular psychiatry · 2025Review
- Challenges of modelling TDP-43 pathology in mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Neural Excitatory/Inhibitory Imbalance in Motor Aging: From Genetic Mechanisms to Therapeutic Challenges.Biology · 2025Review
- TMEM106B deficiency leads to alterations in lipid metabolism and obesity in the TDP-43Communications biology · 2025Article
- Elevated nuclear TDP-43 induces constitutive exon skipping.Molecular neurodegeneration · 2024Article
- Mitochondria: A Promising Convergent Target for the Treatment of Amyotrophic Lateral Sclerosis.Cells · 2024Review
- Sex-Specific Early Retinal Dysfunction in Mutant TDP-43 Transgenic Mice.Journal of Alzheimer's disease : JAD · 2024Article
- Advancements and challenges in amyotrophic lateral sclerosis.Frontiers in neuroscience · 2024Review
- RNA-binding deficient TDP-43 drives cognitive decline in a mouse model of TDP-43 proteinopathy.eLife · 2023Article
- Modulation of the Cellular microRNA Landscape: Contribution to the Protective Effects of High-Density Lipoproteins (HDL).Biology · 2023Review
- TDP-43 knockdown in mouse model of ALS leads to dsRNA deposition, gliosis, and neurodegeneration in the spinal cord.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- The Emerging Role of Mitochondrial Dysfunction in the Pathogenesis of Idiopathic Inflammatory Myopathies.Rambam Maimonides medical journal · 2023Review
- Mitophagy regulation in aging and neurodegenerative disease.Biophysical reviews · 2023Review
- IntelliCage: the development and perspectives of a mouse- and user-friendly automated behavioral test system.Frontiers in behavioral neuroscience · 2023Review
- Disturb mitochondrial associated proteostasis: Neurodegeneration and imperfect ageing.Frontiers in cell and developmental biology · 2023Review
- TDP-43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosis.Translational neurodegeneration · 2022Review
- Status of ALS Treatment, Insights into Therapeutic Challenges and Dilemmas.Journal of personalized medicine · 2022Review
14 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The majority of amyotrophic lateral sclerosis (ALS) cases as well as many patients suffering from frontotemporal lobar dementia (FTLD) with ubiquitinated inclusion bodies show TDP-43 pathology, the protein encoded by the TAR DNA-binding protein (Tardbp) gene. We used recombinase-mediated cassette exchange to introduce an ALS patient cDNA into the mouse Tdp-43 locus. Expression levels of human A315T TDP-43 protein were 300% elevated in heterozygotes, whereas the endogenous mouse Tdp-43 was decreased to 20% of wild type levels as a result of disturbed feedback regulation. Heterozygous TDP-43(A315TKi) mutants lost 10% of their body weight and developed insoluble TDP-43 protein starting as early as 3 months after birth, a pathology that was exacerbated with age. We analyzed the splicing patterns of known Tdp-43 target genes as well as genome-wide gene expression levels in different tissues that indicated mitochondrial dysfunction. In heterozygous mutant animals, we observed a relative decrease in expression of Parkin (Park2) and the fatty acid transporter CD36 along with an increase in fatty acids, HDL cholesterol, and glucose in the blood. As seen in transmission electron microscopy, neuronal cells in motor cortices of TDP-43(A315TKi) animals had abnormal neuronal mitochondrial cristae formation. Motor neurons were reduced to 90%, but only slight motoric impairment was detected. The observed phenotype was interpreted as a predisease model, which might be valuable for the identification of further environmental or genetic triggers of neurodegeneration.
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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.