• Fangfang Yin, Magali Dumont, Rebecca Banerjee, Yao Ma, Huihong Li, Michael T Lin, M Flint Beal, Carl Nathan, Bobby Thomas, and Aihao Ding.
• Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA.
• FASEB J. 2010 Dec 1; 24 (12): 4639-47.

AbstractProgranulin 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.

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