Telomere shortening and metabolic compromise underlie dystrophic cardiomyopathy.

ABSTRACT: Duchenne muscular dystrophy (DMD) is an incurable X-linked genetic disease that is caused by a mutation in the dystrophin gene and affects one in every 3,600 boys. We previously showed that long telomeres protect mice from the lethal cardiac disease seen in humans with the same genetic defect, dystrophin deficiency. By generating the mdx^4cv/mTR^G2 mouse model with "humanized" telomere lengths, the devastating dilated cardiomyopathy phenotype seen in patients with DMD was recapitulated. Here, we analyze the degenerative sequelae that culminate in heart failure and death in this mouse model. We report progressive telomere shortening in developing mouse cardiomyocytes after postnatal week 1, a time when the cells are no longer dividing. This proliferation-independent telo

SUBMITTER: Chang AC 

PROVIDER: S-EPMC5135315 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature