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Publication : A genome-wide library of MADM mice for single-cell genetic mosaic analysis.

First Author  Contreras X Year  2021
Journal  Cell Rep Volume  35
Issue  12 Pages  109274
PubMed ID  34161767 Mgi Jnum  J:306183
Mgi Id  MGI:6715489 Doi  10.1016/j.celrep.2021.109274
Citation  Contreras X, et al. (2021) A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Rep 35
abstractText  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.
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