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Molecular and Cellular Biology, August 2007, p. 5316-5326, Vol. 27, No. 15
0270-7306/07/$08.00+0     doi:10.1128/MCB.00339-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Prolonged Sox4 Expression in Oligodendrocytes Interferes with Normal Myelination in the Central Nervous System ^,

Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg, Erlangen, Germany,¹ Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany,² Institut für Anatomie, Universität Erlangen-Nürnberg, Erlangen, Germany,³ Max-Planck-Institut für Neurobiologie, Martinsried, Germany⁴

Received 26 February 2007/ Returned for modification 28 March 2007/ Accepted 10 May 2007

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.

Published ahead of print on 21 May 2007.

Supplemental material for this article may be found at http://mcb.asm.org/.

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