Red2Flpe-SCON: a versatile, multicolor strategy for generating mosaic conditional knockout mice

Szu-Hsien Sam Wu, Somi Kim, Heetak Lee, Ji-Hyun Lee, So-Yeon Park, Réka Bakonyi, Isaree Teriyapirom, Natalia Hallay, Sandra Pilat-Carotta, Hans-Christian Theussl, Jihoon Kim, Joo-Hyeon Lee, Benjamin D. Simons, Jong Kyoung Kim, Gabriele Colozza () and Bon-Kyoung Koo ()
Additional contact information
Szu-Hsien Sam Wu: Dr. Bohr-Gasse 3
Somi Kim: Pohang University of Science and Technology (POSTECH)
Heetak Lee: Yuseong-gu
Ji-Hyun Lee: Yuseong-gu
So-Yeon Park: Yuseong-gu
Réka Bakonyi: Dr. Bohr-Gasse 3
Isaree Teriyapirom: Dr. Bohr-Gasse 3
Natalia Hallay: Dr. Bohr-Gasse 3
Sandra Pilat-Carotta: Dr. Bohr-Gasse 3
Hans-Christian Theussl: Institute of Molecular Pathology (IMP)
Jihoon Kim: Yuseong-gu
Joo-Hyeon Lee: University of Cambridge
Benjamin D. Simons: University of Cambridge
Jong Kyoung Kim: Pohang University of Science and Technology (POSTECH)
Gabriele Colozza: Dr. Bohr-Gasse 3
Bon-Kyoung Koo: Pohang University of Science and Technology (POSTECH)

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract Image-based lineage tracing enables tissue turnover kinetics and lineage potentials of different adult cell populations to be investigated. Previously, we reported a genetic mouse model system, Red2Onco, which ectopically expressed mutated oncogenes together with red fluorescent proteins (RFP). This system enabled the expansion kinetics and neighboring effects of oncogenic clones to be dissected. We now report Red2Flpe-SCON: a mosaic knockout system that uses multicolor reporters to label both mutant and wild-type cells. We develop the Red2Flpe mouse line for red clone-specific Flpe expression, as well as the FRT-based SCON (Short Conditional IntrON) method to facilitate tunable conditional mosaic knockouts in mice. We use the Red2Flpe-SCON method to study Sox2 mutant clonal analysis in the esophageal epithelium of adult mice which reveal that the stem cell gene, Sox2, is less essential for adult stem cell maintenance itself, but rather for stem cell proliferation and differentiation.

Date: 2024
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DOI: 10.1038/s41467-024-49382-y

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