| RRC ID |
51321
|
| Author |
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.
|
| Title |
Elavl3 is essential for the maintenance of Purkinje neuron axons.
|
| Journal |
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.
|
| Volume |
8(1)
|
| Pages |
2722
|
| Published |
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
|
| Times Cited |
10
|
| Resource |
| DNA material |
CSII-CMV-Venus-Mito-IRES2-Bsd (RDB08118)
CS-CDF-CG-PRE (RDB04379). |
