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-Chen, Ming Tsan Su, Long Sun Ro, Chiung Mei Chen, Hsiu Mei Hsieh-Li*


研究成果: 雜誌貢獻期刊論文同行評審

38 引文 斯高帕斯(Scopus)


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.

頁(從 - 到)288-303
期刊Journal of Neurochemistry
出版狀態已發佈 - 2011 7月

ASJC Scopus subject areas

  • 生物化學
  • 細胞與分子神經科學


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