Type of publication:
Type of document:
Contreras, X; Amberg, N; Davaatseren, A; Hansen, AH; Sonntag, J; Andersen, L; Bernthaler, T; Streicher, C; Heger, A; Johnson, RL; Schwarz, LA; Luo, L; Rülicke, T; Hippenmeyer, S
A genome-wide library of MADM mice for single-cell genetic mosaic analysis.
Cell Rep. 2021; 35(12):109274
Authors Vetmeduni Vienna:
Andersen Lill Kristin
Vetmed Research Units
Institut für In-vivo und In-vitro-Modelle
- Mosaic analysis with double markers (MADM) offers one approach to visualize and concomitantly manipulate genetically defined cells in mice with single-cell resolution. MADM applications include the analysis of lineage, single-cell morphology and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous gene functions in vivo in health and disease. Yet, MADM can only be applied to <25% of all mouse genes on select chromosomes to date. To overcome this limitation, we generate transgenic mice with knocked-in MADM cassettes near the centromeres of all 19 autosomes and validate their use across organs. With this resource, >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic analysis. Beyond a proof of principle, we apply our MADM library to systematically trace sister chromatid segregation in distinct mitotic cell lineages. We find striking chromosome-specific biases in segregation patterns, reflecting a putative mechanism for the asymmetric segregation of genetic determinants in somatic stem cell division.Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.