Journal Article

DZNE-2025-00516

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Loss of Ten1 in mice induces telomere shortening and models human dyskeratosis congenita.

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

2025
Assoc. Washington, DC [u.a.]

This record in other databases:    

Please use a persistent id in citations: doi:10.1126/sciadv.adp8093

Abstract: 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.

Keyword(s): Animals (MeSH) ; Dyskeratosis Congenita: genetics (MeSH) ; Dyskeratosis Congenita: pathology (MeSH) ; Dyskeratosis Congenita: metabolism (MeSH) ; Mice (MeSH) ; Telomere Shortening: genetics (MeSH) ; Disease Models, Animal (MeSH) ; Mice, Knockout (MeSH) ; Humans (MeSH) ; Apoptosis: genetics (MeSH) ; Tumor Suppressor Protein p53: metabolism (MeSH) ; Telomere: genetics (MeSH) ; Telomere: metabolism (MeSH) ; Telomere-Binding Proteins: genetics (MeSH) ; Telomere-Binding Proteins: deficiency (MeSH) ; Signal Transduction (MeSH) ; Tumor Suppressor Protein p53 ; Telomere-Binding Proteins

---

Contributing Institute(s):

1. Translational Biogerontology (AG Ehninger)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2025

---

Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---