Age of onset of RNA toxicity influences phenotypic severity: evidence from an inducible mouse model of myotonic dystrophy (DM1).

ABSTRACT: Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults. It is caused by an expanded (CTG)n tract in the 3' UTR of the Dystrophia Myotonica Protein Kinase (DMPK) gene. This causes nuclear retention of the mutant mRNA into ribonuclear foci and sequestration of interacting RNA-binding proteins (such as muscleblind-like 1 (MBNL1)). More severe congenital and childhood-onset forms of the disease exist but are less understood than the adult disease, due in part to the lack of adequate animal models. To address this, we utilized transgenic mice over-expressing the DMPK 3' UTR as part of an inducible RNA transcript to model early-onset myotonic dystrophy. In mice in which transgene expression was induced during embryogenesis, we found that by two weeks after birth, mice re

SUBMITTER: Gladman JT 

PROVIDER: S-EPMC3764231 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature