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Sanz-Moreno, A. ; Becker, L. ; Xie, K.* ; da Silva Buttkus, P. ; Dragano, N.R.V. ; Aguilar-Pimentel, J.A. ; Amarie, O.V. ; Calzada-Wack, J. ; Kraiger, M. ; Leuchtenberger, S. ; Seisenberger, C. ; Marschall, S. ; Rathkolb, B. ; Scifo, E.* ; Liu, T.* ; Thanabalasingam, A.* ; Sanchez-Vazquez, R.* ; Martinez, P.* ; Blasco, M.A.* ; Savage, S.A.* ; Fuchs, H. ; Ehninger, D.* ; Gailus-Durner, V. ; Hrabě de Angelis, M.

Loss of Ten1 in mice induces telomere shortening and models human dyskeratosis congenita.

Sci. Adv. 11:eadp8093 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Telomere length regulation is essential for genome stability as short telomeres can trigger cellular senescence and apoptosis constituting an integral aspect of biological aging. Telomere biology disorders (TBDs) such as dyskeratosis congenita (DC) are rare, inherited diseases with known mutations in at least 16 different genes encoding components of the telomere maintenance complexes. The precise role of TEN1, part of the CST complex (CTC1, STN1, and TEN1), and the consequences of its loss of function in vivo are not yet known. We investigated the first viable murine model of Ten1 deficiency created by CRISPR-Cas9-mediated exon 3 deletion. Ten1 homozygous knockout mice present with telomere attrition, short life span, skin hyperpigmentation, aplastic anemia, and cerebellar hypoplasia. Molecular analyses revealed a reduction of proliferating cells, increased apoptosis, and stem cell depletion with activation of the p53/p21 signaling pathway. Our data demonstrate that Ten1 deficiency causes telomere shortening and associates with accelerated aging.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Stem-cells; Disease; Complex; Mutations; Biology; Ctc1; Replication; Dysfunction; Mechanisms; Protection
Sprache englisch
Veröffentlichungsjahr 2025
HGF-Berichtsjahr 2025
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Zeitschrift Science Advances
Quellenangaben Band: 11, Heft: 15, Seiten: , Artikelnummer: eadp8093 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort Washington, DC [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
POF Topic(s) 30201 - Metabolic Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500600-001
G-500692-001
Förderungen Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
European Union
Helmholtz Future Topic Aging and Metabolic Programming (AMPro)
German Center for Neurodegenerative Diseases (DZNE)
German Center for Diabetes Research (DZD)
German Federal Ministry of Education and Research
DOI 10.1126/sciadv.adp8093
WOS ID 001464913900008
Scopus ID 105002687159
PubMed ID 40215293
Erfassungsdatum 2025-04-14
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