title: Hypomyelination phenotype caused by impaired differentiation of oligodendrocytes in Emx1-cre mediated Cdk5 conditional knockout mice.
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.
authors.affiliation: Department of Life Science and Medical Bio-Science, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: He
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hashikawa
authors.forename: Ashok B
authors.initials: AB
authors.lastname: Kulkarni
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohshima
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000502:physiology*; D002540:Cerebral Cortex / Q000201:enzymology; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000502:physiology; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000166:cytology*; D010641:Phenotype; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000096:biosynthesis; D014157:Transcription Factors / Q000502:physiology; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D051792:Basic Helix-Loop-Helix Proteins; D051360:Cyclin-Dependent Kinase 5; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D020796:Receptor, Platelet-Derived Growth Factor alpha; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C512773:Olig2 protein, mouse