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Sci Rep. 2018 Feb 9;8(1):2722. doi: 10.1038/s41598-018-21130-5.

Elavl3 is essential for the maintenance of Purkinje neuron axons.

Author information

1
Division of Regenerative Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
2
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
3
Immunoregulation for the treatment of inflammation-related disorders, IBRI Laboratory, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi Chuo-ku, Kobe, 650-0047, Japan.
4
Laboratory for Marmoset Neural Architecture, Brain Science Institute RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
5
Department of Anatomy, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan.
6
Department of Cellular and Molecular Neuropathology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
7
Department of Neurophysiology & Neural Repair, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
8
Research Program for Neural Signaling, Division of Endocrinology, Metabolism and Signal research, Gunma University Initiative for Advanced Research, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
9
Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA.
10
Division of Regenerative Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan. hjokano@jikei.ac.jp.
11
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. hjokano@jikei.ac.jp.

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.

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