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Updated: May 6, 2026

Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers MADM
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MADM-ML, a mouse genetic mosaic system with increased clonal efficiency.

Astra Henner1, P Britten Ventura, Ying Jiang

  • 1Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States of America.

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|October 22, 2013
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Summary

The new MADM-ML system significantly improves cell labeling efficiency compared to the original MADM-SL system. This enhanced Mosaic Analysis with Double Markers (MADM) enables more robust in vivo studies of development and disease.

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Area of Science:

  • Genetics
  • Developmental Biology
  • Cancer Research

Background:

  • Mosaic Analysis with Double Markers (MADM) enables gene knockout and fluorescent labeling of sparse, clonally-related cells in vivo.
  • The original MADM system (MADM-SL) exhibits low clonal efficiency, limiting its application, especially with low Cre expression or small cell populations.
  • Cre/loxP-mediated mitotic recombination in MADM occurs between homologous chromosomes, unlike conditional knockout (CKO).

Purpose of the Study:

  • To compare the recombination efficiency of the novel MADM-ML system with the original MADM-SL system.
  • To evaluate the utility of MADM-ML for creating robust in vivo models of medulloblastoma.
  • To demonstrate the broadened applicability of MADM-ML for cellular-resolution studies in development and disease.

Main Methods:

  • Comparison of recombination efficiency between MADM-ML and MADM-SL using identical Cre transgenes.
  • Establishment of mouse medulloblastoma models utilizing both MADM-SL and MADM-ML systems.
  • Assessment of tumor progression consistency and penetrance in MADM-generated models.

Main Results:

  • MADM-ML demonstrated significantly higher cell labeling efficiency compared to MADM-SL.
  • MADM-SL medulloblastoma models showed variable tumor progression and incomplete penetrance.
  • MADM-ML medulloblastoma models exhibited consistent tumor progression and full penetrance.

Conclusions:

  • MADM-ML offers superior recombination efficiency over MADM-SL.
  • The enhanced efficiency of MADM-ML improves its utility for in vivo studies, including disease modeling.
  • MADM-ML expands the application of MADM for high-resolution biological investigations.