Neurobiology of Disease Loss of -III Spectrin Leads to Purkinje Cell Dysfunction Recapitulating the Behavior and Neuropathology of Spinocerebellar Ataxia Type 5 in Humans
نویسندگان
چکیده
Emma M. Perkins,1 Yvonne L. Clarkson,1 Nancy Sabatier,1 David M. Longhurst,1 Christopher P. Millward,1 Jennifer Jack,1 Junko Toraiwa,1 Mitsunori Watanabe,2 Jeffrey D. Rothstein,3 Alastair R. Lyndon,4 David J. A. Wyllie,1 Mayank B. Dutia,1 and Mandy Jackson1 1The Centre for Integrative Physiology, The University of Edinburgh, George Square, Edinburgh EH8 9XD, United Kingdom, 2Department of Neurology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan, 3Department of Neurology and Neuroscience, Johns Hopkins University, Baltimore, Maryland 21287, and 4School of Life Sciences, Heriot-Watt University, Riccarton, Edinburgh EH14 4AS, United Kingdom
منابع مشابه
Loss of -III Spectrin Leads to Purkinje Cell Dysfunction Recapitulating the Behavior and Neuropathology of Spinocerebellar Ataxia Type 5 in Humans
Citation for published version: Perkins, EM, Clarkson, YL, Sabatier, N, Longhurst, DM, Millward, CP, Jack, J, Toraiwa, J, Watanabe, M, Rothstein, JD, Lyndon, AR, Wyllie, DJA, Dutia, MB & Jackson, M 2010, 'Loss of -III Spectrin Leads to Purkinje Cell Dysfunction Recapitulating the Behavior and Neuropathology of Spinocerebellar Ataxia Type 5 in Humans' The Journal of Neuroscience, vol 30, no. 14,...
متن کاملLoss of beta-III spectrin leads to Purkinje cell dysfunction recapitulating the behavior and neuropathology of spinocerebellar ataxia type 5 in humans.
Mutations in SPTBN2, the gene encoding beta-III spectrin, cause spinocerebellar ataxia type 5 in humans (SCA5), a neurodegenerative disorder resulting in loss of motor coordination. How these mutations give rise to progressive ataxia and what the precise role beta-III spectrin plays in normal cerebellar physiology are unknown. We developed a mouse lacking full-length beta-III spectrin and found...
متن کاملβ-III spectrin underpins ankyrin R function in Purkinje cell dendritic trees: protein complex critical for sodium channel activity is impaired by SCA5-associated mutations
Beta III spectrin is present throughout the elaborate dendritic tree of cerebellar Purkinje cells and is required for normal neuronal morphology and cell survival. Spinocerebellar ataxia type 5 (SCA5) and spectrin associated autosomal recessive cerebellar ataxia type 1 are human neurodegenerative diseases involving progressive gait ataxia and cerebellar atrophy. Both disorders appear to result ...
متن کاملPosterior cerebellar Purkinje cells in an SCA5/SPARCA1 mouse model are especially vulnerable to the synergistic effect of loss of β-III spectrin and GLAST
Clinical phenotypes of spinocerebellar ataxia type-5 (SCA5) and spectrin-associated autosomal recessive cerebellar ataxia type-1 (SPARCA1) are mirrored in mice lacking β-III spectrin (β-III-/-). One function of β-III spectrin is the stabilization of the Purkinje cell-specific glutamate transporter EAAT4 at the plasma membrane. In β-III-/- mice EAAT4 levels are reduced from an early age. In cont...
متن کاملβ-III spectrin is critical for development of purkinje cell dendritic tree and spine morphogenesis.
Mutations in the gene encoding β-III spectrin give rise to spinocerebellar ataxia type 5, a neurodegenerative disease characterized by progressive thinning of the molecular layer, loss of Purkinje cells and increasing motor deficits. A mouse lacking full-length β-III spectrin (β-III⁻/⁻) displays a similar phenotype. In vitro and in vivo analyses of Purkinje cells lacking β-III spectrin, reveal ...
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تاریخ انتشار 2010