Generating in vivo somatic mouse mosaics with locus-specific, stably-integrated transgenic elements

Kim, G. B.; Dutra-Clarke, M.; Levy, R.; Park, H.; Sabet, S.; Molina, J.; Akhtar, A. A.; Bannykh, S.; Danielpour, M.; Breunig, J. J.

doi:10.1101/097386

bioRxiv · 10.1101/097386

Generating in vivo somatic mouse mosaics with locus-specific, stably-integrated transgenic elements

Kim, G. B.·Dutra-Clarke, M.·Levy, R.·Park, H.·Sabet, S.·Molina, J.·Akhtar, A. A.·Bannykh, S.·Danielpour, M.·Breunig, J. J.

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Abstract

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\" driver mutations 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.

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Kim, G. B., Dutra-Clarke, M., Levy, R., Park, H., Sabet, S., Molina, J., Akhtar, A. A., Bannykh, S., Danielpour, M., Breunig, J. J.. 2016-12-30. Generating in vivo somatic mouse mosaics with locus-specific, stably-integrated transgenic elements. https://doi.org/10.1101/097386

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