Does three copies of App contribute to amplified basal interferon signaling in the brain of the Dp1Tyb mouse model of Down syndrome

We have previously found that the Dp1Tyb mouse model of Down syndrome exhibits amplified basal interferon signaling in the brain but that the Dp2Tyb mouse does not unless challenged with interferon. The Dp1Tyb model carries an additional copy of the App gene, whereas the Dp2Tyb model does not. The additional copy of App has been suggested to contribute to altered neuroimmune biology in the brains of a genetically similar DS mouse model. Moreover, raised amyloid-ß triggers interferon signaling in the brain of amyloid accumulation mouse models. Here we test if an additional copy of App contributes to altered interferon signaling in the Dp1Tyb mouse model of Down syndrome in the hippocampus. Overall design: To determine if three-copies of App contribute to amplified basal interferon signaling in the brain of the Dp1Tyb mouse model, we crossed the Dp1Tyb model with heterozygous App knock-out mice, to generate Dp1Tyb mice with three or two-copies of the App gene. We aged these mice to 6-months of age alongside WT controls. Animals were euthanized by perfusion with PBS and hippocampus, cortex and rest of brain isolated. For this study the hippocampus was used for bulk RNA-Seq.