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  • Rapid Generation of Somatic Mouse Mosaics with Locus-Specific, Stably Integrated Transgenic Elements.

Rapid Generation of Somatic Mouse Mosaics with Locus-Specific, Stably Integrated Transgenic Elements.

Cell (2019-09-21)
Gi Bum Kim, David Rincon Fernandez Pacheco, David Saxon, Amy Yang, Sara Sabet, Marina Dutra-Clarke, Rachelle Levy, Ashley Watkins, Hannah Park, Aslam Abbasi Akhtar, Paul W Linesch, Naomi Kobritz, Swasty S Chandra, Katie Grausam, Alberto Ayala-Sarmiento, Jessica Molina, Kristyna Sedivakova, Kendy Hoang, Jeremiah Tsyporin, Daniel S Gareau, Mariella G Filbin, Serguei Bannykh, Chintda Santiskulvong, Yizhou Wang, Jie Tang, Mario L Suva, Bin Chen, Moise Danielpour, Joshua J Breunig
ABSTRACT

In situ transgenesis methods such as viruses and electroporation can rapidly create somatic transgenic mice but lack control over copy number, zygosity, and locus specificity. Here we establish mosaic analysis by dual recombinase-mediated cassette exchange (MADR), which permits stable labeling of mutant cells expressing transgenic elements from precisely defined chromosomal loci. We provide a toolkit of MADR elements for combination labeling, inducible and reversible transgene manipulation, VCre recombinase expression, and transgenesis of human cells. Further, we demonstrate the versatility of MADR by creating glioma models with mixed reporter-identified zygosity or with "personalized" driver mutations from pediatric glioma. MADR is extensible to thousands of existing mouse lines, providing a flexible platform to democratize the generation of somatic mosaic mice. VIDEO ABSTRACT.

MATERIALS
Product Number
Brand
Product Description

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