PDTM-45. INVESTIGATING PEDIATRIC GBM USING IN VIVO SOMATIC MOUSE MOSAICS WITH LOCUS-SPECIFIC, STABLY-INTEGRATED TRANSGENIC ELEMENTS
| Autor: | Kim, Gi Bum, Dutra-Clarke, Marina, Levy, Rachelle, Park, Hannah, Sabet, Sara, Molina, Jessica, Akhtar, Aslam, Bannykh, Serguei, Danielpour, Moise, Breunig, Joshua |
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| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Neuro-Oncology. 19:vi199-vi199 |
| ISSN: | 1523-5866 1522-8517 |
| DOI: | 10.1093/neuonc/nox168.807 |
| Popis: | Viral vectors and electroporation (EP)-mediated gene transfers are efficient means of inducing somatic mosaicism in mice, but they lack the exquisite control over transgene copy number, gene zygosity, and genomic-locus specificity that genetically engineered mouse models (GEMMs) provide. Here, we develop and demonstrate a simple and generalizable in vivo method, mosaic analysis by dual recombinase-mediated cassette exchange (MADR). MADR allows for stable labeling of mutant cells express transgenic elements from a precisely-defined chromosomal locus. To test our method, we generated reporter-labeled lineages from stem and progenitor cells in a well-defined Rosa26mTmG mouse. We demonstrate the power and versatility of MADR by creating novel glioma models with mixed, reporter-defined zygosity or with “personalized,” H3.3-containing driver mutation signatures from pediatric glioma-each manipulation altering the profile of resulting tumors. Thus, MADR provides a high-throughput genetic platform for the dissection of development and disease, and this rapid method can be applied to the thousands of existing gene-trap mice. |
| Databáze: | OpenAIRE |
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