Targeted Deletion of the Antisilencer/Enhancer (ASE) Element from Intron 1 of the Myelin Proteolipid Protein Gene (Plp1) in Mouse Reveals that the Element Is Dispensable for Plp1 Expression in Brain during Development and Remyelination
| Autor: | Neriman T. Kockara, Fanxue Meng, Patricia A. Wight, Baoli Yang, Glauber B. Pereira |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Genetically modified mouse
Male animal structures Monoamine Oxidase Inhibitors Period (gene) Mice Transgenic Biology Transfection Biochemistry Article Cellular and Molecular Neuroscience Cuprizone Mice medicine Animals Remyelination Enhancer Myelin Proteolipid Protein Gene Cell Line Transformed Sequence Deletion Intron Age Factors Brain Gene Expression Regulation Developmental Molecular biology Introns Myelin proteolipid protein Mice Inbred C57BL Disease Models Animal Oligodendroglia medicine.anatomical_structure Enhancer Elements Genetic Animals Newborn Female Demyelinating Diseases |
| Popis: | Myelin proteolipid protein gene (Plp1) expression is temporally regulated in brain, which peaks during the active myelination period of CNS development. Previous studies with Plp1-lacZ transgenic mice demonstrated that (mouse) Plp1 intron 1 DNA is required for high levels of expression in oligodendrocytes. Deletion-transfection analysis revealed the intron contains a single positive regulatory element operative in the N20.1 oligodendroglial cell line, which was named ASE (antisilencer/enhancer) based on its functional properties in these cells. To investigate the role of the ASE in vivo, the element was deleted from the native gene in mouse using a Cre/lox strategy. Although removal of the ASE from Plp1-lacZ constructs profoundly decreased expression in transfected oligodendroglial cell lines (N20.1 and Oli-neu), the element was dispensable to achieve normal levels of Plp1 gene expression in mouse during development (except perhaps at postnatal day 15) and throughout the remyelination period following cuprizone-induced (acute) demyelination. Thus, it is possible that the ASE is non-functional in vivo, or that loss of the ASE from the native gene in mouse can be compensated for by the presence of other regulatory elements within the Plp1 gene. |
| Databáze: | OpenAIRE |
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