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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
Author(s) -
Pereira Glauber B.,
Meng Fanxue,
Kockara Neriman T.,
Yang Baoli,
Wight Patricia A.
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12092
Subject(s) - proteolipid protein 1 , biology , gene , gene expression , myelin , microbiology and biotechnology , enhancer , myelin proteolipid protein , transgene , intron , transfection , regulation of gene expression , genetically modified mouse , genetics , myelin basic protein , central nervous system , endocrinology
Abstract 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 ( a nti s ilencer/ e nhancer) 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.