期刊
FASEB JOURNAL
卷 24, 期 12, 页码 4639-4647出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.10-161471
关键词
neurodegeneration; TDP-43; ubiquitin; transgenic mice
资金
- National Institutes of Health [GM061710, AI030165, NS060885, NS062165]
- Cancer Research Institute
- Appel Established Investigatorship
- William Randolph Hearst Foundation
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 astro-cytes 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.-Yin, F., Dumont, 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
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