A Transgenic Mouse Model to Selectively Identify α Na,K-ATPase Expressing Cells in the Nervous System.

The α Na,K-ATPase (αNKA) is one of four known α isoforms of the mammalian transporter. A deficiency in αNKA is linked to severe movement control disorders. Understanding the pathogenesis of these disorders is limited by an incomplete knowledge of αNKA expression in the brain as well as the challenges associated with identifying living cells that express the isoform for subsequent electrophysiological studies.

The wmN1 enhancer region in intron 1 is required for expression of human PLP1.

The myelin proteolipid protein gene (PLP1) encodes the most abundant protein present in myelin from the central nervous system (CNS). Its expression must be tightly controlled as evidenced by mutations that alter PLP1 dosage; both overexpression (elevated PLP1 copy number) and lack thereof (PLP1 deletion) result in X-linked genetic disorders in man. However, not much is known about the mechanisms that govern expression of the human gene.

Control of human PLP1 expression through transcriptional regulatory elements and alternatively spliced exons in intron 1.

Although the myelin proteolipid protein gene (PLP1) encodes the most abundant protein in central nervous system (CNS) myelin, not much is known about the mechanisms that govern expression of the human gene (hPLP1). Much more is known about the processes that regulate Plp1 gene expression in rodents. From studies with Plp1-lacZ transgenic mice, it was determined that the first intron of mouse Plp1 (mPlp1) is required to attain high levels of expression in brain, concurrent with the active myelination period.

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.

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.