Mice with Pulmonary Fibrosis Driven by Telomere Dysfunction

Cell Rep. 2015 Jul 14;12(2):286-99. doi: 10.1016/j.celrep.2015.06.028. Epub 2015 Jul 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleomycin / toxicity
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • DNA Damage / drug effects
  • DNA Repair / drug effects
  • Disease Models, Animal
  • Female
  • Idiopathic Pulmonary Fibrosis / metabolism
  • Idiopathic Pulmonary Fibrosis / pathology*
  • Lung / diagnostic imaging
  • Lung / metabolism
  • Lung / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Radiography
  • Tamoxifen / pharmacology
  • Telomerase / deficiency
  • Telomerase / genetics
  • Telomere / metabolism*
  • Telomere Shortening
  • Telomeric Repeat Binding Protein 1 / deficiency
  • Telomeric Repeat Binding Protein 1 / genetics
  • Telomeric Repeat Binding Protein 1 / metabolism
  • Tumor Suppressor Protein p53 / metabolism


  • Cyclin-Dependent Kinase Inhibitor p21
  • Telomeric Repeat Binding Protein 1
  • Tumor Suppressor Protein p53
  • Tamoxifen
  • Bleomycin
  • Telomerase