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

[ Vol. 15 , Issue. 1 ]

Author(s):

Qihua Chen, Jinxia Zhou, Cao Huang, Bo Huang, Fangfang Bi, Hongxia Zhou* and Bo Xiao*   Pages 3 - 9 ( 7 )

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.

Affiliation:

Department of Neurology, Xiangya Hospital of Central South University, Changsha 410008, Department of Neurology, Xiangya Hospital of Central South University, Changsha 410008, Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, Department of Neurology, Xiangya Hospital of Central South University, Changsha 410008, Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, Department of Neurology, Xiangya Hospital of Central South University, Changsha 410008



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