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. (21st December 2012)

• Record Type: Journal Article
• Authors: Pereira, Glauber B.; Meng, Fanxue; Kockara, Neriman T.; Yang, Baoli; Wight, Patricia A.
• Is Part Of: Journal of neurochemistry. Volume 124:Number 4(2013:Feb.)
• Page Start: 454
• Page End: 465
• Publication Date: 2012-12-21
• Subjects: Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.12092
• Languages: English
• ISSNs: 0022-3042

Abstract

<abstract abstract-type="main" id="jnc12092-abs-0001"> <title>Abstract</title> <p>Myelin proteolipid protein gene (<italic>Plp1</italic>) expression is temporally regulated in brain, which peaks during the active myelination period of CNS development. Previous studies with <italic>Plp1‐lacZ</italic> transgenic mice demonstrated that (mouse) <italic>Plp1</italic> 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 (<underline>a</underline>nti<underline>s</underline>ilencer/<underline>e</underline>nhancer) based on its functional properties in these cells. To investigate the role of the ASE <italic>in vivo</italic>, the element was deleted from the native gene in mouse using a Cre/<italic>lox</italic> strategy. Although removal of the ASE from <italic>Plp1‐lacZ</italic> constructs profoundly decreased expression in transfected oligodendroglial cell lines (N20.1 and Oli‐neu), the element was dispensable to achieve normal levels of <italic>Plp1</italic> 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 <italic>in vivo</italic>, 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 <italic>Plp1</italic> gene.</p> </abstract>