Dissection of gene function at clonal level using mosaic analysis with double markers

Abstract

MADM (Mosaic Analysis with Double Markers) technology offers a genetic approach in mice to visualize and concomitantly manipulate genetically defined cells at clonal level and single cell resolution. MADM employs Cre recombinase/loxP-dependent interchromosomal mitotic recombination to reconstitute two split marker genes—green GFP and red tdTomato — and can label sparse clones of homozygous mutant cells in one color and wild-type cells in the other color in an otherwise unlabeled background. At present, major MADM applications include lineage tracing, single cell labeling, conditional knockouts in small populations of cells and induction of uniparental chromosome disomy to assess effects of genomic imprinting. MADM can be applied universally in the mouse with the sole limitation being the specificity of the promoter controlling Cre recombinase expression. Here I review recent developments and extensions of the MADM technique and give an overview of the major discoveries and progresses enabled by the implementation of the novel genetic MADM tools.

Key words： MADM; genetic mosaic; clonal analysis; lineage tracing; neural development; genomic imprinting

Acknowledgements

I thank L. Luo and H. Zong for continued discussions about MADM and G. Arque for helpful comments on the manuscript. This work was supported by IST Austria institutional funds.

Compliance with ethics guidelines

Simon Hippenmeyer declares that he has no conflict of interest and that all IST Austria institutional and national guidelines for the care and use of laboratory animals were followed.

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