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
-
The Glutamatergic Neurotransmission in the Central Nervous System
Current Medicinal Chemistry Role of Nitric Oxide Signaling Pathways in Brain Injuries
Current Chemical Biology Soothing the Inflamed Brain: Effect of Non-Steroidal Anti-Inflammatory Drugs on Alzheimers Disease Pathology
CNS & Neurological Disorders - Drug Targets Neuroprotective Effects of Ellagitannins: A Brief Review
Current Drug Targets Role of FK506 Binding Proteins in Neurodegenerative Disorders
Current Medicinal Chemistry Roles and Therapeutic Potential of Metallothioneins in Neurodegenerative Diseases
Current Pharmaceutical Biotechnology The Neurotrophins and Their Role in Alzheimers Disease
Current Neuropharmacology Protein Misfolding in Disease and Small Molecule Therapies
Current Topics in Medicinal Chemistry Induced Pluripotent Stem Cells and Their Potential for Basic and Clinical Sciences
Current Cardiology Reviews Prediction of Gene Co-Expression by Quantifying Heterogeneous Features
Current Bioinformatics Research on the Pathological Mechanism and Drug Treatment Mechanism of Depression
Current Neuropharmacology GSTP1 Polymorphisms and their Association with Glutathione Transferase and Peroxidase Activities in Patients with Motor Neuron Disease
CNS & Neurological Disorders - Drug Targets Meet Our Editorial Board Member
CNS & Neurological Disorders - Drug Targets Commentary [ Research Highlights(To miR or Not to miR: That is the Question in ALS Disease ]
CNS & Neurological Disorders - Drug Targets Bis(thiosemicarbazone) Metal Complexes as Therapeutics for Neurodegenerative Diseases
Current Topics in Medicinal Chemistry Flavonoids as Sirtuin Modulators
Current Topics in Medicinal Chemistry Role of Free Radicals and Poly(ADP-Ribose)Polymerase-1 in the Development of Spinal Cord Injury: New Potential Therapeutic Targets
Current Medicinal Chemistry Proteomic Approaches Contributing to the Understanding of Neurodegenerative Diseases: Focus on Alzheimers Disease
Current Proteomics Human Tooth Germ Stem Cells Preserve Neuro-Protective Effects after Long-Term Cryo-Preservation
Current Neurovascular Research Therapeutic Efficacy of Selegiline in Neurodegenerative Disorders and Neurological Diseases
Current Drug Targets