Figure 1: The Diptheria Toxin (DT) system is a genetic tool for ablating myelinating oligodendrocytes with the goal of understanding the role of these cells in neurophysiology and in various neurological diseases. (A) The cytotoxicity of DTresults from its inhibition of elongation initiation factor 2 (eIF2) which in turn suppresses protein translation. Oligodendrocyte specificity is achieved in one of two ways. In one case (A), an oligodendrocyte-restricted promoter sequence (e.g. pPLP) directs the expression of an inducible Cre recombinase, which upon experimental activation facilitates the expression of the alpha subunit of DT (DT-a) in addition to reporter GFP. The alpha subunit on its own is unable to cross cell membranes and therefore impacts only the cell in which it was induced. In a similar but distinct strategy (B), an oligodendrocyte-restricted promoter sequence (pMBP in this case) drives the expression of a transgenic DT receptor (DTR) in a mouse otherwise resistant to DT, such that treatment with exogenous DT affects only those cells expressing the cognate receptor.