gamma‐secretase is an intramembrane protease composed of four transmembrane proteins: presenilin, nicastrin, Pen‐2, and Aph‐1. Several studies have examined the role of gamma‐secretase in neurons but none have done so in non‐neuronal cells. Therefore, our lab developed a conditional knockout mouse in which gamma‐secretase was conditionally deleted from the myelinating cells of the brain. Here, we use quantitative PCR to confirm the specificity of the conditional deletion and to probe a series of putative genes for their altered expression in conditional knockout mice. Moreover, we begin to look at transcriptional changes in the conditional knockout animals using using RNA‐seq. Grant Funding Source : Supported by National Institute of Neurological Disorders and Stroke grant 1R01NS079796