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


MeSH Major

  • Frontotemporal Dementia
  • Intercellular Signaling Peptides and Proteins


  • 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.

publication date

  • December 2010



  • Academic Article



  • eng

PubMed Central ID

  • PMC2992364

Digital Object Identifier (DOI)

  • 10.1096/fj.10-161471

PubMed ID

  • 20667979

Additional Document Info

start page

  • 4639

end page

  • 47


  • 24


  • 12