Send to

Choose Destination
See comment in PubMed Commons below
FASEB J. 2010 Dec;24(12):4639-47. doi: 10.1096/fj.10-161471. Epub 2010 Jul 28.

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

Author information

  • 1Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA.


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.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center