Sensitivity to neurotoxic stress is not increased in progranulin-deficient mice |
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Authors: | Terri L Petkau Shanshan Zhu Ge Lu Sarah Fernando Max Cynader Blair R Leavitt |
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Institution: | 1. Centre for Molecular Medicine & Therapeutics, Department of Medical Genetics, University of British Columbia, and Children''s and Women''s Hospital, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4;2. Division of Neurology, Department of Medicine, University of British Columbia Hospital, S 192–2211 Wesbrook Mall, Vancouver, BC, Canada V6T 2B5;3. Brain Research Centre, University of British Columbia, Vancouver, BC, Canada, V6T 1Z3 |
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Abstract: | Loss-of-function mutations in the progranulin (GRN) gene are a common cause of autosomal dominant frontotemporal lobar degeneration, a fatal and progressive neurodegenerative disorder common in people less than 65 years of age. In the brain, progranulin is expressed in multiple regions at varying levels, and has been hypothesized to play a neuroprotective or neurotrophic role. Four neurotoxic agents were injected in vivo into constitutive progranulin knockout (Grn−/−) mice and their wild-type (Grn+/+) counterparts to assess neuronal sensitivity to toxic stress. Administration of 3-nitropropionic acid, quinolinic acid, kainic acid, and pilocarpine induced robust and measurable neuronal cell death in affected brain regions, but no differential cell death was observed between Grn+/+ and Grn−/− mice. Thus, constitutive progranulin knockout mice do not have increased sensitivity to neuronal cell death induced by the acute chemical models of neuronal injury used in this study. |
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Keywords: | Progranulin Frontotemporal lobar degeneration Frontotemporal dementia Progranulin knockout mouse Neurotoxin 3-Nitropropionic acid Kainic acid Quinolinic acid Pilocarpine |
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