Behavioral deficits and progressive neuropathology in progranulin-deficient mice: A mouse model of frontotemporal dementia

Fangfang Yin, Magali Dumont, Rebecca Banerjee, Yao Ma, Huihong Li, Michael T. Lin, M. Flint Beal, Carl Nathan, Bobby Thomas, Aihao Ding

Research output: Contribution to journalArticlepeer-review

123 Scopus citations

Abstract

Progranulin haploinsufficiency causes frontotemporal dementia with tau-negative, ubiquitin-positive neuronal inclusion pathology. In this study, we showed that progranulin-deficient mice displayed increased depression- and disinhibition-like behavior, as well as deficits in social recognition from a relatively young age. These mice did not have any deficit in locomotion or exploration. Eighteen-month-old progranulin-deficient mice demonstrated impaired spatial learning and memory in the Morris water maze. In addition to behavioral deficits, progranulin-deficient mice showed a progressive development of neuropathology from 12 mo of age, including enhanced activation of microglia and astrocytes and ubiquitination and cytoplasmic accumulation of phosphorylated TDP-43. Thus, progranulin deficiency induced FTD-like behavioral and neuropathological deficits. These mice may serve as an important tool for deciphering underlying mechanisms in frontotemporal dementia.

Original languageEnglish (US)
Pages (from-to)4639-4647
Number of pages9
JournalFASEB Journal
Volume24
Issue number12
DOIs
StatePublished - Dec 2010

Keywords

  • Neurodegeneration
  • TDP-43
  • Transgenic mice
  • Ubiquitin

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint

Dive into the research topics of 'Behavioral deficits and progressive neuropathology in progranulin-deficient mice: A mouse model of frontotemporal dementia'. Together they form a unique fingerprint.

Cite this