A cell type-specific allele of the POU gene Oct-6 reveals Schwann cell autonomous function in nerve development and regeneration
January 2002
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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) reveals 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.
- Male
- Animals
- Female
- Research Support, Non-U.S. Gov't
- Mice
- Crosses, Genetic
- DNA-Binding Proteins/metabolism
- Sequence Deletion
- Chimera
- Organ Specificity
- Alleles
- Gene Targeting
- Cell Lineage
- Myelin Sheath/physiology
- Octamer Transcription Factor-6
- Schwann Cells/*physiology
- Early Growth Response Protein 2
- Nerve Regeneration/*physiology
- Nerve Tissue Proteins/genetics/physiology
- Peripheral Nerves/anatomy & histology/*growth & development
- Transcription Factors/genetics/metabolism/*physiology
- *Enhancer Elements (Genetics)/genetics
- schwann
- oct -6
- nerve
- schwann cells
- expression
- oct -6 expression
- -6dsce
- oct -6dsce mice
- allele
- animal
- level
- development
- schwann cell lineage
- oct -6dsce animals
- figure
- -20
- schwann cell differentiation
- protein
- myelin
- dsce allele