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Transcriptome Analysis of Conditional Knockout Mice

Gamma‐secretase is an intramembrane protein that cleaves type I transmembrane proteins. It is known to be involved in Alzheimer's disease and neurodevelopment. Previous studies have investigated the role of gamma‐secretase role in neurons. However, it has seldom been considered in glial cells, the non‐neuronal cells of the brain. Here, a conditional knockout mouse was made in which Nicastrin, a substrate receptor for gamma‐secretase, was rendered nonfunctional in oligodendrocytes. These mice displayed schizophrenia‐ and compulsive‐like phenotypes. In order to identify genes and pathways that elicit these phenotypes, RNA‐Seq was used to perform transcriptome analysis searching for differentially expressed genes in the experimental mice. Gene ontology programs were used to evaluate the genes and identify biological processes that may play a role in the behavioral aspects of these mice. Disease pathways identified in the analysis include Alzheimer's disease, myelination, schizophrenia, and oligodendrocyte function. Cellular pathways include extracellular communication and immune responses. Together this analysis presents a picture of the cellular pathways involved in the non‐cognitive aspects of Alzheimer's disease as it relates to the non‐neuronal white matter of the brain.