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Patterned Purkinje cell loss in the ataxic sticky mouse

2011; Wiley; Volume: 34; Issue: 1 Linguagem: Inglês

10.1111/j.1460-9568.2011.07725.x

1460-9568

Justyna R. Sarna, Richard Hawkes,

Neuroscience and Neuropharmacology Research

European Journal of NeuroscienceVolume 34, Issue 1 p. 79-86 Patterned Purkinje cell loss in the ataxic sticky mouse Justyna R. Sarna, Justyna R. Sarna Department of Clinical Neurosciences, Movement Disorders Program, Health Sciences Centre, 3330 Hospital Drive N.W., Calgary, AB T2N 4N1, CanadaSearch for more papers by this authorRichard Hawkes, Richard Hawkes Department of Cell Biology & Anatomy, Hotchkiss Brain Institute, and Genes and Development Research Group, Faculty of Medicine, University of Calgary, Calgary, AB, CanadaSearch for more papers by this author Justyna R. Sarna, Justyna R. Sarna Department of Clinical Neurosciences, Movement Disorders Program, Health Sciences Centre, 3330 Hospital Drive N.W., Calgary, AB T2N 4N1, CanadaSearch for more papers by this authorRichard Hawkes, Richard Hawkes Department of Cell Biology & Anatomy, Hotchkiss Brain Institute, and Genes and Development Research Group, Faculty of Medicine, University of Calgary, Calgary, AB, CanadaSearch for more papers by this author First published: 06 June 2011 https://doi.org/10.1111/j.1460-9568.2011.07725.xCitations: 19 Dr J. R. Sarna, as above. E-mail: [email protected] Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract The ataxic sticky (sti/sti) mouse is a spontaneous autosomal recessive mutant resulting from a disruption in the editing domain of the alanyl-tRNA synthetase (Aars) gene. The sticky phenotype is characterized by a small body size, a characteristic unkempt coat and neurological manifestations including marked tremor and ataxia starting at 6 weeks of age. The present study was undertaken to examine the spatiotemporal features of Purkinje cell degeneration in the sticky mouse. Purkinje cell loss was found to be both progressive and patterned, with vermal lobules VI, IX and X, crus 1 of the hemisphere, and the flocculus and paraflocculus being differentially resistant to degeneration. The pattern of Purkinje cell degeneration in sticky is not random – in general, the sphingosine kinase 1a-immunonegative Purkinje cell subset is preferentially susceptible to early cell death. In addition, zebrin II/aldolase C expression in the sticky cerebellum is profoundly downregulated, whereas the heat-shock protein 25 is both ectopically expressed in some scattered Purkinje cells and downregulated in other Purkinje cells in which it is normally expressed constitutively. Compared with many mouse mutants with patterned Purkinje cell death, in which successive stripes of cell loss are very clear, Purkinje cell loss in sticky shows a less clear-cut pattern between different Purkinje cell subtypes, with the result that preferential survival is less dramatic. This may represent a secondary consequence of the downregulation of zebrin II expression. References Ahn, A.H., Dziennis, S., Hawkes, R. & Herrup, K. (1994) The cloning of zebrin II reveals its identity with aldolase C. Development, 120, 2081–2090. CASPubMedWeb of Science®Google Scholar Apps, R. & Hawkes, R. (2009) Cerebellar cortical organization: a one-map hypothesis. Nat. Rev. Neurosci., 10, 670–681. 10.1038/nrn2698 CASPubMedWeb of Science®Google Scholar Armstrong, C.L. & Hawkes, R. (2000) Pattern formation in the cerebellar cortex. Biochem. Cell Biol., 78, 551–562. 10.1139/o00-071 CASPubMedWeb of Science®Google Scholar Armstrong, C.L., Krueger-Naug, A.M., Currie, R.W. & Hawkes, R. 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