Abstract
Background: Mutant transactive response DNA-binding protein (TDP-43) is closely correlated to the inherited form of amyotrophic lateral sclerosis (ALS). TDP-43 transgenic rats can reproduce the core phenotype of ALS and constitutive expression of TDP-43 caused postnatal death.
Objective: The study aimed to understand whether neurologic deficiency caused by mutant TDP- 43 is dependent on its temporal expression.
Method: Transgenic rats were established that express mutant human TDP-43 (M337V substitution) in neurons, then a Tet-off system was used to regulate its expression.
Results: TDP-43 mutant transgenic rats developed significant weakness after the transgene was activated. Rats with expression of mutant TDP-43 at 30 days showed a more aggressive phenotype. More severe pathological changes in neurogenic atrophy were observed in these rats.
Conclusion: Temporal expression of mutant TDP-43 in neurons promoted serious phenotype in rats. The dysfunction of TDP-43 had a profound impact on the development of motor neurons and skeletal muscles.
Keywords: Amyotrophic Lateral Sclerosis (ALS), TAR DNA-binding protein 43, motor neurons, transgenic rats, CAG, Tetresponsive transactivator.
Current Neurovascular Research
Title:Temporal Expression of Mutant TDP-43 Correlates with Early Amyotrophic Lateral Sclerosis Phenotype and Motor Weakness
Volume: 15 Issue: 1
Author(s): Qihua Chen, Jinxia Zhou, Cao Huang, Bo Huang, Fangfang Bi, Hongxia Zhou*Bo Xiao*
Affiliation:
- Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107,United States
- Department of Neurology, Xiangya Hospital of Central South University, Changsha 410008,China
Keywords: Amyotrophic Lateral Sclerosis (ALS), TAR DNA-binding protein 43, motor neurons, transgenic rats, CAG, Tetresponsive transactivator.
Abstract: Background: Mutant transactive response DNA-binding protein (TDP-43) is closely correlated to the inherited form of amyotrophic lateral sclerosis (ALS). TDP-43 transgenic rats can reproduce the core phenotype of ALS and constitutive expression of TDP-43 caused postnatal death.
Objective: The study aimed to understand whether neurologic deficiency caused by mutant TDP- 43 is dependent on its temporal expression.
Method: Transgenic rats were established that express mutant human TDP-43 (M337V substitution) in neurons, then a Tet-off system was used to regulate its expression.
Results: TDP-43 mutant transgenic rats developed significant weakness after the transgene was activated. Rats with expression of mutant TDP-43 at 30 days showed a more aggressive phenotype. More severe pathological changes in neurogenic atrophy were observed in these rats.
Conclusion: Temporal expression of mutant TDP-43 in neurons promoted serious phenotype in rats. The dysfunction of TDP-43 had a profound impact on the development of motor neurons and skeletal muscles.
Export Options
About this article
Cite this article as:
Chen Qihua, Zhou Jinxia, Huang Cao, Huang Bo, Bi Fangfang, Zhou Hongxia*, Xiao Bo*, Temporal Expression of Mutant TDP-43 Correlates with Early Amyotrophic Lateral Sclerosis Phenotype and Motor Weakness, Current Neurovascular Research 2018; 15 (1) . https://dx.doi.org/10.2174/1567202615666180109161541
DOI https://dx.doi.org/10.2174/1567202615666180109161541 |
Print ISSN 1567-2026 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5739 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
TRP Channels: New Potential Therapeutic Approaches in CNS Neuropathies
CNS & Neurological Disorders - Drug Targets The Pharmacokinetics and Toxicology of Aluminum in the Brain
Current Inorganic Chemistry (Discontinued) C. elegans as Model for Drug Discovery
Current Topics in Medicinal Chemistry Editorial (Thematic Issue: New Therapeutic Bearings for Repositioned Drugs)
Current Topics in Medicinal Chemistry Nanoparticle-Based Gene Therapy Intervention for Stroke Treatment: A Systematic Review
Current Gene Therapy The Quest for Novel Biomarkers in Early Diagnosis of Diabetic Neuropathy
Current Proteomics Preclinical Safety and Pharmacokinetic Profile of 3K3A-APC, a Novel, Modified Activated Protein C for Ischemic Stroke
Current Pharmaceutical Design Inhibition of Human Serine Racemase, an Emerging Target for Medicinal Chemistry
Current Drug Targets Water and Ion Channels: Crucial in the Initiation and Progression of Apoptosis in Central Nervous System?
Current Neuropharmacology Antiinflammatory Activity of Melatonin in Central Nervous System
Current Neuropharmacology Recent Patents on Novel P2X7 Receptor Antagonists and their Potential for Reducing Central Nervous System Inflammation
Recent Patents on CNS Drug Discovery (Discontinued) Mesenchymal Stem Cells: New Approaches for the Treatment of Neurological Diseases
Current Stem Cell Research & Therapy Frontotemporal Lobar Degeneration (FTLD): Review and Update for Clinical Neurologists
Current Alzheimer Research Brain: The Potential Diagnostic and Therapeutic Target for Glaucoma
CNS & Neurological Disorders - Drug Targets Attenuating Muscle Wasting: Cell and Gene Therapy Approaches
Current Genomics Thiopurine Biotransformation and Pharmacological Effects: Contribution of Oxidative Stress
Current Drug Metabolism Histological and Direct Evidence for the Role of Complement in the Neuroinflammation of AD
Current Alzheimer Research Melanocortins As Innovative Drugs for Ischemic Diseases and Neurodegenerative Disorders: Established Data and Perspectives
Current Medicinal Chemistry Withanolides: Biologically Active Constituents in the Treatment of Alzheimer’s Disease
Medicinal Chemistry Astrocytes Pathology in ALS: A Potential Therapeutic Target?
Current Pharmaceutical Design