PUBLICATION

Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo

Authors
Hsieh, J.Y., Ulrich, B.N., Issa, F.A., Lin, M.A., Brown, B., Papazian, D.M.
ID
ZDB-PUB-200710-22
Date
2020
Source
eLIFE   9: (Journal)
Registered Authors
Lin, Meng-Chin, Papazian, Diane M.
Keywords
neuroscience, zebrafish
MeSH Terms
  • Disease Models, Animal
  • Age Factors
  • Animals
  • Purkinje Cells/physiology*
  • Mutation*
  • Zebrafish
  • Spinocerebellar Ataxias/congenital*
  • Spinocerebellar Ataxias/genetics
  • Zebrafish Proteins/genetics*
  • Cell Survival/genetics*
  • Cerebellum/growth & development
  • Shaw Potassium Channels/genetics*
(all 12)
PubMed
32644043 Full text @ Elife
Abstract
Mutations in KCNC3, which encodes the Kv3.3 K+ channel, cause spinocerebellar ataxia 13 (SCA13). SCA13 exists in distinct forms with onset in infancy or adulthood. Using zebrafish, we tested the hypothesis that infant- and adult-onset mutations differentially affect the excitability and viability of Purkinje cells in vivo during cerebellar development. An infant-onset mutation dramatically and transiently increased Purkinje cell excitability, stunted process extension, impaired dendritic branching and synaptogenesis, and caused rapid cell death during cerebellar development. Reducing excitability increased early Purkinje cell survival. In contrast, an adult-onset mutation did not significantly alter basal tonic firing in Purkinje cells, but reduced excitability during evoked high frequency spiking. Purkinje cells expressing the adult-onset mutation matured normally and did not degenerate during cerebellar development. Our results suggest that differential changes in the excitability of cerebellar neurons contribute to the distinct ages of onset and timing of cerebellar degeneration in infant- and adult-onset SCA13.
Genes / Markers
Figures
Figure Gallery (16 images) / 2
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
la118TgTransgenic Insertion
    1 - 1 of 1
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    Human Disease / Model
    Human Disease Fish Conditions Evidence
    spinocerebellar ataxia type 13TAS
    1 - 1 of 1
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    Sequence Targeting Reagents
    No data available
    Fish
    No data available
    Antibodies
    No data available
    Orthology
    No data available
    Engineered Foreign Genes
    Marker Marker Type Name
    VenusEFGVenus
    1 - 1 of 1
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    Mapping
    No data available
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    Citation
    Hsieh, J.Y., Ulrich, B.N., Issa, F.A., Lin, M.A., Brown, B., Papazian, D.M. (2020) Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo. eLIFE. 9:.