PT  - JOURNAL ARTICLE
AU  - Contreras, Ximena
AU  - Davaatseren, Amarbayasgalan
AU  - Amberg, Nicole
AU  - Hansen, Andi H.
AU  - Sonntag, Johanna
AU  - Andersen, Lill
AU  - Bernthaler, Tina
AU  - Heger, Anna
AU  - Johnson, Randy
AU  - Schwarz, Lindsay A.
AU  - Luo, Liqun
AU  - Rülicke, Thomas
AU  - Hippenmeyer, Simon
TI  - A Genome-wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis
AID  - 10.1101/2020.06.05.136192
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.05.136192
4099  - http://biorxiv.org/content/early/2020/06/06/2020.06.05.136192.short
4100  - http://biorxiv.org/content/early/2020/06/06/2020.06.05.136192.full
AB  - Mosaic Analysis with Double Markers (MADM) offers a unique 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 could only be applied to <25% of all mouse genes on select chromosomes thus far. To overcome this limitation, we generated transgenic mice with knocked-in MADM cassettes near the centromeres of all 19 autosomes and validated their use across organs. With this resource, >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic analysis. Beyond proof-of-principle, we applied our MADM library to systematically trace sister chromatid segregation in distinct mitotic cell lineages. We found striking chromosome-specific biases in segregation patterns, reflecting a putative mechanism for the asymmetric segregation of genetic determinants in somatic stem cell division.Competing Interest StatementThe authors have declared no competing interest.