期刊
CURRENT NEUROVASCULAR RESEARCH
卷 15, 期 1, 页码 3-9出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1567202615666180109161541
关键词
Amyotrophic Lateral Sclerosis (ALS); TAR DNA-binding protein 43; motor neurons; transgenic rats; CAG; Tetresponsive transactivator
资金
- Natural Science Foundation of China [81401065, 81760238, 81571256]
- science fund for young scientists from Xiangya Hospital of China [2013Q09]
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.
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