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 language | English (US) |
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Pages (from-to) | 4639-4647 |
Number of pages | 9 |
Journal | FASEB Journal |
Volume | 24 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2010 |
Keywords
- Neurodegeneration
- TDP-43
- Transgenic mice
- Ubiquitin
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics