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