RRC ID 51321
著者 Ogawa Y, Kakumoto K, Yoshida T, Kuwako KI, Miyazaki T, Yamaguchi J, Konno A, Hata J, Uchiyama Y, Hirai H, Watanabe M, Darnell RB, Okano H, Okano HJ.
タイトル Elavl3 is essential for the maintenance of Purkinje neuron axons.
ジャーナル Sci Rep
Abstract Neuronal Elav-like (nElavl or neuronal Hu) proteins are RNA-binding proteins that regulate RNA stability and alternative splicing, which are associated with axonal and synaptic structures. nElavl proteins promote the differentiation and maturation of neurons via their regulation of RNA. The functions of nElavl in mature neurons are not fully understood, although Elavl3 is highly expressed in the adult brain. Furthermore, possible associations between nElavl genes and several neurodegenerative diseases have been reported. We investigated the relationship between nElavl functions and neuronal degeneration using Elavl3-/- mice. Elavl3-/- mice exhibited slowly progressive motor deficits leading to severe cerebellar ataxia, and axons of Elavl3-/- Purkinje cells were swollen (spheroid formation), followed by the disruption of synaptic formation of axonal terminals. Deficit in axonal transport and abnormalities in neuronal polarity was observed in Elavl3-/- Purkinje cells. These results suggest that nElavl proteins are crucial for the maintenance of axonal homeostasis in mature neurons. Moreover, Elavl3-/- mice are unique animal models that constantly develop slowly progressive axonal degeneration. Therefore, studies of Elavl3-/- mice will provide new insight regarding axonal degenerative processes.
巻・号 8(1)
ページ 2722
公開日 2018-2-9
DOI 10.1038/s41598-018-21130-5
PII 10.1038/s41598-018-21130-5
PMID 29426875
PMC PMC5807307
MeSH Animals Axonal Transport Axons / metabolism Axons / pathology* Cells, Cultured Cerebellar Ataxia / etiology* Cerebellar Ataxia / metabolism Cerebellar Ataxia / pathology ELAV-Like Protein 3 / physiology* Gene Expression Regulation Kinesins / genetics Kinesins / metabolism Mice Mice, Inbred C57BL Mice, Inbred ICR Mice, Knockout Motor Disorders / etiology* Motor Disorders / metabolism Motor Disorders / pathology Nerve Degeneration / etiology* Nerve Degeneration / metabolism Nerve Degeneration / pathology Neurons / metabolism Neurons / pathology* Purkinje Cells / metabolism Purkinje Cells / pathology*
IF 3.998
引用数 10
リソース情報
遺伝子材料 CSII-CMV-Venus-Mito-IRES2-Bsd (RDB08118) CS-CDF-CG-PRE (RDB04379).