Temporal Expression of Mutant TDP-43 Correlates with Early Amyotrophic Lateral Sclerosis Phenotype and Motor Weakness

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.

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