EMBO J. 2002 Sep
Ghazvini M, Mandemakers W, Jaegle M, Piirsoo M, Driegen S, Koutsourakis M, Smit X, Grosveld F, Meijer D
Abstract
While an important role for the POU domain transcription factor Oct-6 in the developing peripheral nerve has been well established, studies into its exact role in nerve development and regeneration have been hampered by the high mortality rate of newborn Oct-6 mutant animals. In this study we have generated a Schwann cell-specific Oct-6 allele through deletion of the Schwann cell-specific enhancer element (SCE) in the Oct-6 locus. Analysis of mice homozygous for this allele (deltaSCE allele) rev
...[more]eals that rate-limiting levels of Oct-6 in Schwann cells are dependent on the SCE and that this element does not contribute to Oct-6 regulation in other cell types. We demonstrate a Schwann cell autonomous function for Oct-6 during nerve development as well as in regenerating nerve. Additionally, we show that Krox-20, an important regulatory target of Oct-6 in Schwann cells, is activated, with delayed kinetics, through an Oct-6-independent mechanism in these mice.
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Mesh Headings:
Alleles, Animals, Cell Lineage, Chimera, Crosses, Genetic, DNA-Binding Proteins, Early Growth Response Protein 2, Enhancer Elements, Genetic, Female, Gene Targeting, Male, Mice, Myelin Sheath, Nerve Regeneration, Nerve Tissue Proteins, Octamer Transcription Factor-6, Organ Specificity, Peripheral Nerves, Schwann Cells, Sequence Deletion, Transcription Factors