title: Sensitivity to neurotoxic stress is not increased in progranulin-deficient mice.
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.
authors.affiliation: 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.
authors.forename: Terri L
authors.initials: TL
authors.lastname: Petkau
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhu
authors.forename: Ge
authors.initials: G
authors.lastname: Lu
authors.forename: Sarah
authors.initials: S
authors.lastname: Fernando
authors.forename: Max
authors.initials: M
authors.lastname: Cynader
authors.forename: Blair R
authors.initials: BR
authors.lastname: Leavitt
mesh_terms: D000818:Animals; D005452:Fluoresceins; D000077155:Granulins; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency*; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D018345:Mice, Knockout; D020258:Neurotoxicity Syndromes / Q000150:complications / Q000209:etiology* / Q000235:genetics*; D009498:Neurotoxins / Q000633:toxicity*; D009574:Nitro Compounds / Q000633:toxicity; D000077153:Progranulins; D011422:Propionates / Q000633:toxicity; D017378:Quinolinic Acid / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced
chemical_list: D005452:Fluoresceins; D000077155:Granulins; C120204:Grn protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D009498:Neurotoxins; D009574:Nitro Compounds; D000077153:Progranulins; D011422:Propionates; C435731:fluoro jade; D017378:Quinolinic Acid; C015392:3-nitropropionic acid; D007608:Kainic Acid
keywords: 3-Nitropropionic acid; Frontotemporal dementia; Frontotemporal lobar degeneration; Kainic acid; Neurotoxin; Pilocarpine; Progranulin; Progranulin knockout mouse; Quinolinic acid