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

Progranulin haploinsufficiency causes frontotemporal dementia with tau‐negative, ubiq‐uitin‐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 astro‐cytes and ubiquitination and cytoplasmic accumulation of phosphorylated TDP‐43. Thus, progranulin deficiency induced FTD‐like behavioral and neuro‐pathological deficits. These mice may serve as an important tool for deciphering underlying mechanisms in frontotemporal dementia.—Yin, F., Du‐mont, M., Banerjee, R., Ma, Y., Li, H., Lin, M. T., Beal, M. F., Nathan, C., Thomas, B., Ding, A. Behavioral deficits and progressive neuropathology in progranulin‐deficient mice: a mouse model of frontotemporal dementia. FASEB J. 24, 4639–4647 (2010). www.fasebj.org