Mice with Pulmonary Fibrosis Driven by Telomere Dysfunction.
Idiopathic pulmonary fibrosis (IPF) is a degenerative disease of the lungs with an average survival post-diagnosis of 2-3 years. New therapeutic targets and treatments are necessary. Mutations in components of the telomere-maintenance enzyme telomerase or in proteins important for telomere protectio...
| Autores: | , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/10312 |
| Acceso en línea: | http://hdl.handle.net/20.500.12105/10312 |
| Access Level: | acceso abierto |
| Palabra clave: | Animals Cyclin-Dependent Kinase Inhibitor p21 DNA Damage DNA Repair Disease Models, Animal Female Idiopathic Pulmonary Fibrosis Lung Male Mice Mice, Inbred C57BL Mice, Knockout Radiography Tamoxifen Telomerase Telomere Telomere Shortening Telomeric Repeat Binding Protein 1 Failure |
| Sumario: | Idiopathic pulmonary fibrosis (IPF) is a degenerative disease of the lungs with an average survival post-diagnosis of 2-3 years. New therapeutic targets and treatments are necessary. Mutations in components of the telomere-maintenance enzyme telomerase or in proteins important for telomere protection are found in both familial and sporadic IPF cases. However, the lack of mouse models that faithfully recapitulate the human disease has hampered new advances. Here, we generate two independent mouse models that develop IPF owing to either critically short telomeres (telomerase-deficient mice) or severe telomere dysfunction in the absence of telomere shortening (mice with Trf1 deletion in type II alveolar cells). We show that both mouse models develop pulmonary fibrosis through induction of telomere damage, thus providing proof of principle of the causal role of DNA damage stemming from dysfunctional telomeres in IPF development and identifying telomeres as promising targets for new treatments. |
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