TMOD-08. INVESTIGATING PEDIATRIC GBM USING IN VIVO SOMATIC MOUSE MOSAICS WITH LOCUS-SPECIFIC, STABLY-INTEGRATED TRANSGENIC ELEMENTS

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2017-06, Vol.19 (suppl_4), p.iv50-iv50
• Main Authors: Kim, Gi Bum, Dutra-Clarke, Marina, Levy, Rachelle, Park, Hannah, Sabet, Sara, Molina, Jessica, Akhtar, Aslam Abbasi, Danielpour, Moise, Breunig, Joshua
• Format: Article
• Language: English
• Subjects: Abstracts
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/nox083.207

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 speci-ficity 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 Rosa26 mTmG 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.