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@ARTICLE{SanzMoreno:277989,
author = {Sanz-Moreno, Adrián and Becker, Lore and Xie, Kan and da
Silva-Buttkus, Patricia and Dragano, Nathalia R V and
Aguilar-Pimentel, Antonio and Amarie, Oana V and
Calzada-Wack, Julia and Kraiger, Markus and Leuchtenberger,
Stefanie and Seisenberger, Claudia and Marschall, Susan and
Rathkolb, Birgit and Scifo, Enzo and Liu, Ting and
Thanabalasingam, Anoja and Sanchez-Vazquez, Raul and
Martinez, Paula and Blasco, Maria A and Savage, Sharon A and
Fuchs, Helmut and Ehninger, Dan and Gailus-Durner, Valérie
and de Angelis, Martin Hrabê},
title = {{L}oss of {T}en1 in mice induces telomere shortening and
models human dyskeratosis congenita.},
journal = {Science advances},
volume = {11},
number = {15},
issn = {2375-2548},
address = {Washington, DC [u.a.]},
publisher = {Assoc.},
reportid = {DZNE-2025-00516},
pages = {eadp8093},
year = {2025},
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.},
keywords = {Animals / Dyskeratosis Congenita: genetics / Dyskeratosis
Congenita: pathology / Dyskeratosis Congenita: metabolism /
Mice / Telomere Shortening: genetics / Disease Models,
Animal / Mice, Knockout / Humans / Apoptosis: genetics /
Tumor Suppressor Protein p53: metabolism / Telomere:
genetics / Telomere: metabolism / Telomere-Binding Proteins:
genetics / Telomere-Binding Proteins: deficiency / Signal
Transduction / Tumor Suppressor Protein p53 (NLM Chemicals)
/ Telomere-Binding Proteins (NLM Chemicals)},
cin = {AG Ehninger},
ddc = {500},
cid = {I:(DE-2719)1013005},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40215293},
pmc = {pmc:PMC11988282},
doi = {10.1126/sciadv.adp8093},
url = {https://pub.dzne.de/record/277989},
}