Neuroprotective effects of granulocyte-colony stimulating factor in a novel transgenic mouse model of SCA17

Ya Chin Chang, Cheng Yueh Lin, Chen Ming Hsu, Hsin Chieh Lin, Yu Hsiang Chen, Guey-Jen Lee, Ming-Tsan Su, Long Sun Ro, Chiung Mei Chen, Hsiu Mei Hsieh

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant inherited disorder characterized by degeneration of spinocerebellar tracts and selected brainstem neurons owing to the expansion of a CAG repeat of the human TATA-binding protein (hTBP) gene. To gain insight into the pathogenesis of this hTBP mutation, we generated transgenic mice with the mutant hTBP gene driven by the Purkinje specific protein (Pcp2/L7) gene promoter. Mice with the expanded hTBP allele developed ataxia within 2-5 months. Behavioral analysis of L7-hTBP transgenic mice showed reduced fall latency in a rotarod assay. Purkinje cell degeneration was identified by immunostaining of calbindin and IP3R1. Reactive gliosis and neuroinflammation occurred in the transgenic cerebellum, accompanied by up-regulation of GFAP and Iba1. The L7-hTBP transgenic mice were thus confirmed to recapitulate the SCA17 phenotype and were used as a disease model to explore the potential of granulocyte-colony stimulating factor in SCA17 treatment. Our results suggest that granulocyte-colony stimulating factor has a neuroprotective effect in these transgenic mice, ameliorating their neurological and behavioral deficits. These data indicate that the expression of the mutant hTBP in Purkinje cells is sufficient to produce cell degeneration and an ataxia phenotype, and constitutes a good model for better analysis of the neurodegeneration in SCA17.

Original languageEnglish
Pages (from-to)288-303
Number of pages16
JournalJournal of Neurochemistry
Volume118
Issue number2
DOIs
Publication statusPublished - 2011 Jul 1

Fingerprint

TATA-Box Binding Protein
Neuroprotective Agents
Granulocyte Colony-Stimulating Factor
Transgenic Mice
Genes
Purkinje Cells
Ataxia
Spinocerebellar Tracts
Rotarod Performance Test
Phenotype
Calbindins
Gliosis
Spinocerebellar Ataxia 17
Cerebellum
Brain Stem
Neurons
Assays
Up-Regulation
Alleles
Mutation

Keywords

  • G-CSF
  • Purkinje cell
  • SCA17
  • cerebellum
  • spinocerebellar ataxia

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Neuroprotective effects of granulocyte-colony stimulating factor in a novel transgenic mouse model of SCA17. / Chang, Ya Chin; Lin, Cheng Yueh; Hsu, Chen Ming; Lin, Hsin Chieh; Chen, Yu Hsiang; Lee, Guey-Jen; Su, Ming-Tsan; Ro, Long Sun; Chen, Chiung Mei; Hsieh, Hsiu Mei.

In: Journal of Neurochemistry, Vol. 118, No. 2, 01.07.2011, p. 288-303.

Research output: Contribution to journalArticle

Chang, Ya Chin ; Lin, Cheng Yueh ; Hsu, Chen Ming ; Lin, Hsin Chieh ; Chen, Yu Hsiang ; Lee, Guey-Jen ; Su, Ming-Tsan ; Ro, Long Sun ; Chen, Chiung Mei ; Hsieh, Hsiu Mei. / Neuroprotective effects of granulocyte-colony stimulating factor in a novel transgenic mouse model of SCA17. In: Journal of Neurochemistry. 2011 ; Vol. 118, No. 2. pp. 288-303.
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