title: Neurological disturbances, premature lethality, and central myelination deficiency in transgenic mice overexpressing the homeo domain transcription factor Oct-6.
abstract: Pit, Oct, Unc (POU) homeo domain transcription factors have been implicated in various developmental processes, including cell division, differentiation, specification, and survival of specific cell types. Although expression of the transcription factor Oct-6 in oligodendroglia is confined to the promyelin stage and is downregulated at the myelin stage of development, the effect of Oct-6 overexpression on oligodendrocyte development has not been established. Here we show that transgenic animals overexpressing Oct-6 at late oligodendrocyte development develop a severe neurologic syndrome characterized by action tremors, recurrent seizures, and premature death. Axons in the central nervous system of Oct-6 transgenics were hypomyelinated, hypermyelinated, or dysmyelinated, and ultrastructural analyses suggested that myelin formation was premature. The vulnerability of developing oligodendroglia to Oct-6 deregulation provides evidence that the POU factor may play a direct role in myelin disease pathogenesis in the mammalian CNS.
authors.affiliation: Department of Medical Biochemistry, University of Aarhus, 8000 Aarhus C, Denmark. naj@biobase.dk
authors.forename: N A
authors.initials: NA
authors.lastname: Jensen
authors.forename: K M
authors.initials: KM
authors.lastname: Pedersen
authors.forename: J E
authors.initials: JE
authors.lastname: Celis
authors.forename: M J
authors.initials: MJ
authors.lastname: West
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D015152:Blotting, Northern; D015153:Blotting, Western; D002490:Central Nervous System / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D003001:Cloning, Molecular; D004247:DNA / Q000032:analysis / Q000235:genetics; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D016254:Mutagenesis, Insertional; D004676:Myelin Basic Protein / Q000235:genetics* / Q000378:metabolism; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism; D009422:Nervous System Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D050816:Octamer Transcription Factor-6; D016133:Polymerase Chain Reaction; D012313:RNA / Q000032:analysis / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004676:Myelin Basic Protein; C494180:Pou3f1 protein, mouse; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6; D012313:RNA; D004247:DNA