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EMBO J ; 21(17): 4612-20, 2002 Sep 02.
Article in English | MEDLINE | ID: mdl-12198163

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) 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.


Subject(s)
Enhancer Elements, Genetic , Nerve Regeneration/physiology , Peripheral Nerves/growth & development , Schwann Cells/physiology , Transcription Factors/physiology , Alleles , Animals , Cell Lineage , Chimera , Crosses, Genetic , DNA-Binding Proteins/metabolism , Early Growth Response Protein 2 , Enhancer Elements, Genetic/genetics , Female , Gene Targeting , Male , Mice , Myelin Sheath/physiology , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/physiology , Octamer Transcription Factor-6 , Organ Specificity , Peripheral Nerves/anatomy & histology , Sequence Deletion , Transcription Factors/genetics , Transcription Factors/metabolism
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