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

Cell Rep. 2021 Jun 22;35(12):109274. doi: 10.1016/j.celrep.2021.109274.


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.

Keywords: Mosaic Analysis with Double Markers (MADM); functional gene analysis; genetic mosaic; genomic imprinting; lineage; single cell; sister chromatid Segregation Pattern; stem cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli / metabolism
  • Adult Stem Cells / metabolism
  • Animals
  • Chromatids / genetics
  • Chromosome Segregation
  • Chromosomes, Mammalian / genetics
  • Disease Models, Animal
  • Gene Library*
  • Genetic Markers
  • Genome*
  • Genomic Imprinting
  • Liver / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Mitosis
  • Models, Biological
  • Mosaicism*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Phenotype
  • Recombination, Genetic / genetics
  • Single-Cell Analysis*
  • Stem Cell Niche
  • Uniparental Disomy


  • Genetic Markers