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11	Generierung und Analyse EMA/E2F-6-defizienter Mäuse Pohlers, Michael 12 December 2005 (has links) The present study focuses on the biological functions of the transcription factor EMA/E2F-6, a member of the E2F-family of transcription factors that play an import role in cell cycle progression, differentiation and apoptosis. EMA/E2F-6 functions as a transcriptional repressor by recruiting a large protein complex, that includes polycomb group proteins, to specific target genes in order to silence their expression. To identify the biological functions of EMA/E2F-6 mice lacking this factor were developed and subsequently analysed. EMA/E2F6-/- mice are born with the expected frequency, are fertile and develop normally up to 18 months of age. Then about 25 % of these mice develop a paralysis of the hind limbs and present with a severe primary myelination defect of the spinal cord (and in part of peripheral nerves, too) that is accompanied by a massive infiltration of macrophages. Importantly, the histological findings were also detected in EMA/E2F-6-/- mice lacking clinical symptoms albeit to a lesser extend. With respect to EMA/E2F-6 association with polycomb group (Pc-G) proteins there were no significant findings such as skeletal transformations. In addition, only a mild proliferation defect of T-lymphocytes was observed that, in a more severe form, is typical for Pc-G mutations in the mice. Surprisingly, embryonic fibroblasts from EMA/E2F-6-/- mice have no obvious cell cycle defects. Accordingly, gene expression profiles showed that classical E2F target genes were normally regulated in these cells. However, EMA/E2F-6-/- fibroblasts ubiquitously express genes like alpha-tubulin-3 and -7 that are normally expressed in a strictly testis-specific manner. All EMA/E2F-6-dependent target genes identified contain a conserved E2F-binding site in their promoters that is required both for EMA/E2F-6 binding and regulation. Zellzyklus Demyelinisierungen Gehirnveränderungen Geninaktivierung Gewebsspezifische Genexpression Lähmungen Makrophageninfiltration Mäuse/Nullmutanten Neuronenuntergang Oligodendrozytenreduktion Polycomb-Gruppe-Proteine Proliferation von T-Lymphozyten Regulation der Genexpression Rückenmarksveränderungen Skeletttransformationen Transkriptionsfaktoren Brain/Abnormalities Cell Cycle Demyelinisations Gene Targeting Infiltration of Makrophages Mice/Knockout Neuron Death Paralyses Polycomb-Group Proteins Proliferation of T-Lymphocytes Reduktion of Oligodendrocytes Regulation of Gene Expression Skeletal Transformations Spinal Cord/Abnormalities Tissue-specific Gene Expression Transkription Factors 570 Biowissenschaften, Biologie 32 Biologie WG 3580 WG 3700 ddc:570

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Generierung und Analyse EMA/E2F-6-defizienter Mäuse