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Hypomyelination Phenotype Caused by Impaired Differentiation of Oligodendrocytes in Emx1-cre Mediated Cdk5 Conditional Knockout Mice

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Abstract

Cyclin-dependent kinase 5 (Cdk5) plays a pivotal role in neuronal migration and differentiation, and in axonal elongation. Although many studies have been conducted to analyze neuronal functions of Cdk5, its kinase activity has also been reported during oligodendrocyte differentiation, which suggests Cdk5 may play an important role in oligodendrocytes. Here, we describe a hypomyelination phenotype observed in Emx1-cre mediated Cdk5 conditional knockout (cKO) mice (Emx1-cKO), in which the Cdk5 gene was deleted in neurons, astrocytes and oligodendrocyte -lineage cells. In contrast, the Cdk5 gene in CaMKII cKO mice was deleted only in neurons. Because the development of mature oligodendrocytes from oligodendrocyte precursor cells is a complex process, we performed in situ hybridization using markers for the oligodendrocyte precursor cell and for the differentiated oligodendrocyte. Our results indicate that hypomyelination in Emx1-cKO is due to the impaired differentiation of oligodendrocytes, rather than to the proliferation or migration of their precursors. The present study confirmed the in vivo role of Cdk5 in oligodendrocyte differentiation.

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Acknowledgments

We wish to thank Drs. Itohara and Iwasato for providing the Emx1-cre mice, and Drs. Dragatsis and Zeitlin for providing the CamKII-cre mice. We would also like to thank Dr. Elias Utreras and Eric Contreras for critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Life Science and Medical Bio-Science, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan

    Xiaojuan He & Toshio Ohshima

  2. Department of Pediatrics, Asahikawa Medical College, Asahikawa, 078-8510, Japan

    Satoru Takahashi

  3. Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN , Saitama, 351-0198, Japan

    Hiromi Suzuki & Katsuhiko Mikoshiba

  4. Support Unit for Neuromorphological Analysis, Brain Science Institute, RIKEN, Saitama, 351-0198, Japan

    Tsutomu Hashikawa

  5. Functional Genomics Section, Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA

    Ashok B. Kulkarni

Authors
  1. Xiaojuan He
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  2. Satoru Takahashi
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  3. Hiromi Suzuki
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  4. Tsutomu Hashikawa
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  5. Ashok B. Kulkarni
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  6. Katsuhiko Mikoshiba
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  7. Toshio Ohshima
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Correspondence to Toshio Ohshima.

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Special Issue: In Honor of Dr. Mikoshiba.

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He, X., Takahashi, S., Suzuki, H. et al. Hypomyelination Phenotype Caused by Impaired Differentiation of Oligodendrocytes in Emx1-cre Mediated Cdk5 Conditional Knockout Mice. Neurochem Res 36, 1293–1303 (2011). https://doi.org/10.1007/s11064-010-0391-0

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  • DOI: https://doi.org/10.1007/s11064-010-0391-0

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