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bioRxiv · 10.1101/2020.06.05.136192

A Genome-wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis

Contreras, X.·Davaatseren, A.·Amberg, N.·Hansen, A. H.·Sonntag, J.·Andersen, L.·Bernthaler, T.·Heger, A.·Johnson, R.·Schwarz, L. A.·Luo, L.·Ruelicke, T.·Hippenmeyer, S.
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Abstract

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.

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Contreras, X., Davaatseren, A., Amberg, N., Hansen, A. H., Sonntag, J., Andersen, L., Bernthaler, T., Heger, A., Johnson, R., Schwarz, L. A., Luo, L., Ruelicke, T., Hippenmeyer, S.. 2020-06-06. A Genome-wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis. https://doi.org/10.1101/2020.06.05.136192

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