| Literature DB >> 31539496 |
Gi Bum Kim1, David Rincon Fernandez Pacheco1, David Saxon1, Amy Yang1, Sara Sabet2, Marina Dutra-Clarke1, Rachelle Levy1, Ashley Watkins1, Hannah Park2, Aslam Abbasi Akhtar2, Paul W Linesch2, Naomi Kobritz1, Swasty S Chandra1, Katie Grausam1, Alberto Ayala-Sarmiento1, Jessica Molina1, Kristyna Sedivakova1, Kendy Hoang3, Jeremiah Tsyporin3, Daniel S Gareau4, Mariella G Filbin5, Serguei Bannykh6, Chintda Santiskulvong7, Yizhou Wang7, Jie Tang7, Mario L Suva8, Bin Chen3, Moise Danielpour9, Joshua J Breunig10.
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.Entities:
Keywords: AAVS1 locus; Brainbow; CRISPR/Cas9 base editors; MADR MAX; RMCE; VCre; ependymoma; epigenetics; scATAC-seq; scRNA-seq
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Year: 2019 PMID： 31539496 PMCID： PMC6934691 DOI： 10.1016/j.cell.2019.08.013
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582