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

Autor: Wu SS; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, 1030, Vienna, Austria.; Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, Vienna, Austria., Kim S; Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea., Lee H; Center for Genome Engineering, Institute for Basic Science, Expo-ro 55, Yuseong-gu, Daejeon, 34126, Republic of Korea., Lee JH; Center for Genome Engineering, Institute for Basic Science, Expo-ro 55, Yuseong-gu, Daejeon, 34126, Republic of Korea., Park SY; Center for Genome Engineering, Institute for Basic Science, Expo-ro 55, Yuseong-gu, Daejeon, 34126, Republic of Korea., Bakonyi R; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, 1030, Vienna, Austria., Teriyapirom I; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, 1030, Vienna, Austria.; Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, Vienna, Austria., Hallay N; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, 1030, Vienna, Austria., Pilat-Carotta S; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, 1030, Vienna, Austria., Theussl HC; IMP/IMBA Transgenic Service, Institute of Molecular Pathology (IMP), Vienna, Austria., Kim J; Center for Genome Engineering, Institute for Basic Science, Expo-ro 55, Yuseong-gu, Daejeon, 34126, Republic of Korea.; Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, South Korea., Lee JH; Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK., Simons BD; Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.; The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.; Department of Applied Mathematics and Theoretical Physics, Centre for Mathematical Sciences, Wilberforce Road, Cambridge, CB3 0WA, UK., Kim JK; Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea., Colozza G; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, 1030, Vienna, Austria. gabriele.colozza@imba.oeaw.ac.at., Koo BK; Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea. koobk@ibs.re.kr.; Center for Genome Engineering, Institute for Basic Science, Expo-ro 55, Yuseong-gu, Daejeon, 34126, Republic of Korea. koobk@ibs.re.kr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jun 11; Vol. 15 (1), pp. 4963. Date of Electronic Publication: 2024 Jun 11.
DOI: 10.1038/s41467-024-49382-y
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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