Genetically modified mouse

Somatic cell

Gene

Cell biology

Biology

Transgene

Genetics

Locus (genetics)

Cell

Highlights•MADR enables single-locus somatic genetic modification and lineage tracing in vivo•MADR can be used to interrogate the dosage response of transgenes in vivo•MADR allows "personalized" brain tumor modeling in vivo via CRISPR variants or transgenes•MADR is adaptable to hundreds of available mouse linesSummaryIn 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 mut...

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