Loss of Ten1 in mice induces telomere shortening and models human dyskeratosis congenita.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40215293.
- Also identified by DOI 10.1126/sciadv.adp8093 and PMC identifier 11988282.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>Ten1</i> deficiency created by CRISPR-Cas9-mediated exon 3 deletion. <i>Ten1</i> 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.
Medical subject headings
- Dyskeratosis Congenita
- Telomere Shortening
- Telomere-Binding Proteins