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RNA-sequencing of mice 24 hours following acute p53 activation due to Mdm2-loss (Mdm2FM/- Cag-CreERTg (FMTg)) compared to mice that retain Mdm2 (Mdm2+/- Cag-CreERTg (Tg))

ABSTRACT: FMTg (Mdm2FM/- Cag-CreERTg) and Tg (Mdm2+/- Cag-CreERTg) mice were administered 6mg/40g of Tamoxifen dissolved in corn-oil and sacrificed 24 hours after injection. Tissues were flash frozen and RNA was isolated using TriZOL reagent as per manufacturers protocols. The goal of this study is to understand the differences and similarities between the p53 transcriptome in various murine tissues

ORGANISM(S): Mus musculus

PROVIDER: GSE151571 | GEO | 2020/08/24

REPOSITORIES: GEO

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Project description:Huntingtons disease (HD) is a devastating neurodegenerative disease, with out effective treatment. Despite significant advances, our understanding of how an expanded CAG repeat in the amino terminus of the large ubiquitously expressed HD gene product remains incomplete. Augmented adult neurogenesis in response to acute and chronic injury, including Huntingtons disease, has been demonstrated, but its role development, disease, and recovery is largely unknown, as are the factors controlling it. The HD gene product, huntingtin (htt) is know to interact with a number of transcription factors which subsequently influence gene expression. Understanding the factors involved in controlling neurogenesis in response to disease would bridge a significant knowledge gap and have tremendous therapeutic potential. We propose to identify transcripts responsible for CAG repeat facilitated neurogenesis. Our hypothesis is that expanded CAG repeats in the Huntingtons disease gene facilitates neurogenesis by altering transcription of genes critical in neurogenesis. We have developed a model in which mouse embryonic stem cells (ESC) with expanded CAG repeats have facilitated neurogenesis. In this model more ESC with expanded CAG repeats transition to neuronal precursors and then develop into mature neurons more rapidly than control ESC. We propose to compare the gene expression profiles between ESC with expanded CAG repeats and control ESCs on days 4 and 6 of neuronal differentiation. Initial studies indicate that key transcriptional differences are occurring at these time points. Control ECS and a an ESC line with150 CAG repeats will be differentiated in triplicate, and RNA isolated form each replicate. It is anticipated that comparison of gene expression between the control and CAG repeat lines at each time point will identify transcripts involved in CAG repeat facilitated neurogenesis. Observed differences at day 4 may be more relevant to the transition from ESC to neuronal precursor whereas differences at day 6 may be more relevant to the neuronal precursor to neuron transition. Keywords: time-course

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Dataset Information

RNA-sequencing of mice 24 hours following acute p53 activation due to Mdm2-loss (Mdm2FM/- Cag-CreERTg (FMTg)) compared to mice that retain Mdm2 (Mdm2+/- Cag-CreERTg (Tg))

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