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Type of publication: Journal Article
Type of document: Full Paper

Year: 2021

Authors: Contreras, X; Amberg, N; Davaatseren, A; Hansen, AH; Sonntag, J; Andersen, L; Bernthaler, T; Streicher, C; Heger, A; Johnson, RL; Schwarz, LA; Luo, L; Rülicke, T; Hippenmeyer, S

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

Source: Cell Rep. 2021; 35(12):109274



Authors Vetmeduni Vienna:

Andersen Lill Kristin
Bernthaler Tina
Rülicke Thomas

Vetmed Research Units
Institut für In-vivo und In-vitro-Modelle


Abstract:
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.Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.


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