Tmod-08. Investigating Pediatric Gbm Using in Vivo Somatic Mouse Mosaics With Locus-specific, Stably-integrated Transgenic Elements
Year: 2017
Type: conference-abstract
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 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 Rosa26mTmG 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.
Source: Neuro-Oncology
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2618382953