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• W2091207278 abstract "Abstract We describe the genetic and neurological features of toppler , a spontaneous autosomal mutation that appeared in a colony of FVB/N mice and that manifests as severe ataxia appearing at around 12 days of age, worsening with age. The lifespan of affected mice is 8–12 months, with occasional mice living longer. Both homozygous males and females are fertile, and females are able to nurture litters. Histological examination of brain revealed no striking abnormalities other than the loss of cerebellar Purkinje cells. The toppler mutation was mapped to mouse chromosome 8, and to assess whether it was novel or a recurrence of a previously described chromosome 8 mouse mutant, toppler mice were crossed with the nervous and tottering mouse mutants. These studies demonstrate that toppler is a unique mouse mutation. Purkinje cell abnormalities in toppler mice were obvious around postnatal day (P) 14, i.e., toppler Purkinje cells already exhibited abnormal morphology. Staining for calbindin, a calcium binding protein enriched in Purkinje cells, showed altered dendritic morphology. Between P14 and P30, dramatic Purkinje cell loss occurred, although there were differences in the degree of Purkinje cell loss in each lobule. At P30, the surviving Purkinje cells expressed zebrin II. From P30 through 6 months, many of the remaining Purkinje cells gradually degenerated. Purkinje cell loss was analyzed by terminal deoxynucleotidyl transferase‐mediated biotinylated UTP nick end labeling (TUNEL), and Purkinje cells were TUNEL‐positive most abundantly at P21. In addition, Bergmann glia were TUNEL positive at P21, and they expressed activated caspase‐3 at earlier time points. Interestingly, despite the apparent death of some Bergmann glia, there was up‐regulation of glial fibrillary acidic protein, expressed in astrocytes as well as Bergmann glia. Given the changes in both Purkinje cells and glia in toppler cerebellum, this may be a very useful model in which to investigate the developmental interaction of Purkinje cells and Bergmann glia. J. Comp. Neurol. 476:113–129, 2004. © 2004 Wiley‐Liss, Inc." @default.
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• W2091207278 date "2004-07-02" @default.
• W2091207278 modified "2023-10-18" @default.
• W2091207278 title "The <i>toppler</i> mouse: A novel mutant exhibiting loss of Purkinje cells" @default.
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• W2091207278 doi "https://doi.org/10.1002/cne.20206" @default.
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