Suppression of progranulin expression leads to formation of intranuclear TDP-43 inclusions in vitro: A cell model of frontotemporal lobar degeneration

Jiuling Zhu, Ning Wang, Xianan Li, Xiaojing Zheng, Junli Zhao, Haibin Xia*, Qinwen Mao

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Mutations in the GRN gene coding for progranulin (PGRN) are responsible for many cases of familial frontotemporal lobar degeneration (FTLD) with TAR DNA-binding protein 43 (TDP-43)-positive inclusions (FTLD-TDP). GRN mutations create null alleles resulting in decreased progranulin protein or haploinsufficiency. FTLD-TDP with GRN mutations is characterized by lentiform neuronal intranuclear inclusions that are positive for TDP-43 in affected brain regions. In this study, by stably expressed short hairpin RNA, we established a neuroblastoma cell line with decreased PGRN level. This cell line reveals TDP-43-positive intranuclear inclusions. In addition, replacement with purified PGRN protein restores normal TDP-43 nuclear distribution. This cell model can be valuable for the study of the role of PGRN in the pathogenesis in FTLD-TDP.

Original languageEnglish (US)
Pages (from-to)1124-1129
Number of pages6
JournalJournal of neuropathology and experimental neurology
Volume78
Issue number12
DOIs
StatePublished - Dec 1 2019

Keywords

  • Cell model
  • Frontotemporal lobar degeneration
  • GRN
  • Progranulin
  • Replacement
  • Short hairpin RNAs
  • TAR DNA binding protein-43

ASJC Scopus subject areas

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

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