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HuC KOマウスにおける軸索輸送障害の可視化
Visualization of the axonal transport dysfunction in HuC KO mouse

  • P2-320
  • 小川 優樹 / Yuki Ogawa:1 長谷川 実奈美 / Minami Hasegawa:1 角元 恭子 / Kyoko Kakumoto:2 吉田 哲 / Tetsu Yoshida:2 Darnell Robert / Robert Darnell:3 岡野 栄之 / Hideyuki Okano:2 岡野 ジェイムス洋尚 / Hirotaka Ja Okano:1 
  • 1:東京慈恵会医科大学 再生医学研究部 / Div Regen Med, Jikei Univ Sch of Med, Tokyo 2:慶應義塾大学 医学部 生理学 / Dept Physiol, Keio Univ Sch of Med, Tokyo 3:ロックフェラー大学 / The Rockefeller Univ, NY, USA 

Hu Proteins (the neuronal Elav-like: nElavl) are the mammalian homologue of the Drosophila Elav, an RNA-binding protein expressed in the nervous system. Hu proteins bind to immature mRNAs and regulate alternative splicing and translation process. Almost all of the brain regions express HuC together with HuB and/or HuD, however cerebellar purkinje cells (PCs) express only HuC. If HuC gene is knocked out, PCs exhibit the phenotype specifically. Cerebellar dysfunction in HuC KO mice leads the intentional tremor, gain abnormality and ataxia at 7 months of age. Prior to the onset, the axons of PCs underwent morphological changes; swollen (called spheroid) and retracted at the deep cerebellar nuclei, although the pathological changes were not observed during cerebellar development. However surprisingly, PCs soma seemed to be intact even at 21 months, which is almost the mouse life span. Though the relationship between HuC reduction and neurodegenerative disease is not reported yet, these symptoms have similarity with spinocerebellar ataxia, parkinson's disease in many aspects. Therefore studying the phenotype of HuC KO mouse's PCs will give us new insight about neurodegenerative process.
First electron microscopy revealed the spheroid was filled with mitochondria, membrane, and some other cellular component. Immunostaining also revealed accumulation of mitochondria and APP in the spheroid. These phenomena indicated impairment of axonal transport. Next we cultured PCs at dissociated condition. Cultured PCs also exhibited spheroid and accumulation of mitochondria. To visualize axonal transport in live cells, we constructed mitochondria targeted photo-convertible fluorescent protein

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