Transcriptomopathies of pre- and post-symptomatic frontotemporal dementia-like mice with TDP-43 depletion in forebrain neurons

Lien Szu Wu, Wei Cheng Cheng, Chia Ying Chen, Ming Che Wu, Yi Chi Wang, Yu Hsiang Tseng, Trees Juen Chuang, Che-Kun Shen

研究成果: 雜誌貢獻文章同行評審

10 引文 斯高帕斯(Scopus)


TAR DNA-binding protein (TDP-43) is a ubiquitously expressed nuclear protein, which participates in a number of cellular processes and has been identified as the major pathological factor in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here we constructed a conditional TDP-43 mouse with depletion of TDP-43 in the mouse forebrain and find that the mice exhibit a whole spectrum of age-dependent frontotemporal dementia-like behaviour abnormalities including perturbation of social behaviour, development of dementia-like behaviour, changes of activities of daily living, and memory loss at a later stage of life. These variations are accompanied with inflammation, neurodegeneration, and abnormal synaptic plasticity of the mouse CA1 neurons. Importantly, analysis of the cortical RNA transcripts of the conditional knockout mice at the pre-/post-symptomatic stages and the corresponding wild type mice reveals age-dependent alterations in the expression levels and RNA processing patterns of a set of genes closely associated with inflammation, social behaviour, synaptic plasticity, and neuron survival. This study not only supports the scenario that loss-of-function of TDP-43 in mice may recapitulate key behaviour features of the FTLD diseases, but also provides a list of TDP-43 target genes/transcript isoforms useful for future therapeutic research.
期刊Acta neuropathologica communications
出版狀態已發佈 - 三月 29 2019

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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