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dc.contributor.authorZumbrennen-Bullough, Kimberly B.en_US
dc.contributor.authorBecker, Loreen_US
dc.contributor.authorGarrett, Lillianen_US
dc.contributor.authorHölter, Sabine M.en_US
dc.contributor.authorCalzada-Wack, Juliaen_US
dc.contributor.authorMossbrugger, Ilonaen_US
dc.contributor.authorQuintanilla-Fend, Leticiaen_US
dc.contributor.authorRacz, Ildikoen_US
dc.contributor.authorRathkolb, Birgiten_US
dc.contributor.authorKlopstock, Thomasen_US
dc.contributor.authorWurst, Wolfgangen_US
dc.contributor.authorZimmer, Andreasen_US
dc.contributor.authorWolf, Eckharden_US
dc.contributor.authorFuchs, Helmuten_US
dc.contributor.authorGailus-Durner, Valerieen_US
dc.contributor.authorde Angelis, Martin Hraběen_US
dc.contributor.authorRomney, Steven J.en_US
dc.contributor.authorLeibold, Elizabeth A.en_US
dc.date.accessioned2014-07-07T17:04:23Z
dc.date.issued2014en_US
dc.identifier.citationZumbrennen-Bullough, K. B., L. Becker, L. Garrett, S. M. Hölter, J. Calzada-Wack, I. Mossbrugger, L. Quintanilla-Fend, et al. 2014. “Abnormal Brain Iron Metabolism in Irp2 Deficient Mice Is Associated with Mild Neurological and Behavioral Impairments.” PLoS ONE 9 (6): e98072. doi:10.1371/journal.pone.0098072. http://dx.doi.org/10.1371/journal.pone.0098072.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12406813
dc.description.abstractIron Regulatory Protein 2 (Irp2, Ireb2) is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2−/− mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc), expression are increased and decreased, respectively, in the brain from Irp2−/− mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0098072en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045679/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and Life Sciencesen
dc.subjectGeneticsen
dc.subjectMolecular Biologyen
dc.subjectNeuroscienceen
dc.subjectOrganismsen
dc.titleAbnormal Brain Iron Metabolism in Irp2 Deficient Mice Is Associated with Mild Neurological and Behavioral Impairmentsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorZumbrennen-Bullough, Kimberly B.en_US
dc.date.available2014-07-07T17:04:23Z
dc.identifier.doi10.1371/journal.pone.0098072*
dash.authorsorderedfalse
dash.contributor.affiliatedZumbrennen-Bullough, Kimberly B.


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