期刊
JOURNAL OF NEUROSCIENCE
卷 36, 期 14, 页码 4106-4120出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3529-15.2016
关键词
alternative splicing; axoglial junctions; myelin; neurofascin; Quaking; RNA-binding proteins
资金
- Multiple Sclerosis Society of Canada
RNA binding proteins required for the maintenance of myelin and axoglial junctions are unknown. Herein, we report that deletion of the Quaking (QKI) RNA binding proteins in oligodendrocytes (OLs) using Olig2-Cre results in mice displaying rapid tremors at postnatal day 10, followed by death at postnatal week 3. Extensive CNS hypomyelination was observed as a result of OL differentiation defects during development. The QKI proteins were also required for adult myelin maintenance, because their ablation using PLP-CreERT resulted in hindlimb paralysis with immobility at similar to 30 d after 4-hydroxytamoxifen injection. Moreover, deterioration of axoglial junctions of the spinal cord was observed and is consistent with a loss of Neurofascin 155 (Nfasc155) isoform that we confirmed as an alternative splice target of the QKI proteins. Our findings define roles for the QKI RNA binding proteins in myelin development and maintenance, as well as in the generation of Nfasc155 to maintain healthy axoglial junctions.
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