title: Prolonged Sox4 expression in oligodendrocytes interferes with normal myelination in the central nervous system.
abstract: The highly related transcription factors Sox4 and Sox11 are both expressed in oligodendrocyte precursors. Yet whether they have a function in oligodendrocyte development is unknown. By overexpressing Sox4 under the control of 3.1 kb of 5' flanking sequences of the myelin basic protein gene in transgenic mice, we extended Sox4 expression in the oligodendrocyte lineage from oligodendrocyte precursors to cells undergoing terminal differentiation. As a consequence of transgene expression, mice develop the full spectrum of phenotypic traits associated with a severe hypomyelination during the first postnatal weeks. Myelin gene expression was severely reduced, and myelin dramatically thinned in several central nervous system (CNS) regions. Despite these disturbances in CNS myelination, the number of oligodendrocytic cells remained unaltered. Considering that apoptosis rates were normal and proliferation only slightly increased, oligodendrocytes likely persist in a premyelinating to early myelinating state. This shows that prolonged Sox4 expression in cells of the oligodendrocyte lineage is incompatible with the acquisition of a fully mature phenotype and argues that the presence of Sox4, and possibly Sox11, in oligodendrocyte precursors may normally prevent premature differentiation.
authors.affiliation: Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg, Fahrstrasse 17, 91054 Erlangen, Germany.
authors.forename: Michaela R
authors.initials: MR
authors.lastname: Potzner
authors.forename: Carola
authors.initials: C
authors.lastname: Griffel
authors.forename: Elke
authors.initials: E
authors.lastname: Lütjen-Drecoll
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bösl
authors.forename: Michael
authors.initials: M
authors.lastname: Wegner
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Sock
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D002490:Central Nervous System / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D003337:Corpus Callosum / Q000378:metabolism; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000378:metabolism; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D055751:SOXC Transcription Factors; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D015534:Trans-Activators / Q000235:genetics*; D019076:Transgenes
chemical_list: D006609:High Mobility Group Proteins; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D012333:RNA, Messenger; D055751:SOXC Transcription Factors; C490793:Sox11 protein, mouse; C489990:Sox4 protein, mouse; D015534:Trans-Activators