Long telomeres protect against age-dependent cardiac disease caused by NOTCH1 haploinsufficiency.

ABSTRACT: Diseases caused by gene haploinsufficiency in humans commonly lack a phenotype in mice that are heterozygous for the orthologous factor, impeding the study of complex phenotypes and critically limiting the discovery of therapeutics. Laboratory mice have longer telomeres relative to humans, potentially protecting against age-related disease caused by haploinsufficiency. Here, we demonstrate that telomere shortening in NOTCH1-haploinsufficient mice is sufficient to elicit age-dependent cardiovascular disease involving premature calcification of the aortic valve, a phenotype that closely mimics human disease caused by NOTCH1 haploinsufficiency. Furthermore, progressive telomere shortening correlated with severity of disease, causing cardiac valve and septal disease in the neonate that was sim

SUBMITTER: Theodoris CV 

PROVIDER: S-EPMC5409071 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature