Inducible and reversible phenotypes in a novel mouse model of Friedreich's Ataxia.

ABSTRACT: Friedreich's ataxia (FRDA), the most common inherited ataxia, is caused by recessive mutations that reduce the levels of frataxin (FXN), a mitochondrial iron binding protein. We developed an inducible mouse model of Fxn deficiency that enabled us to control the onset and progression of disease phenotypes by the modulation of Fxn levels. Systemic knockdown of Fxn in adult mice led to multiple phenotypes paralleling those observed in human patients across multiple organ systems. By reversing knockdown after clinical features appear, we were able to determine to what extent observed phenotypes represent reversible cellular dysfunction. Remarkably, upon restoration of near wild-type FXN levels, we observed significant recovery of function, associated pathology and transcri

SUBMITTER: Chandran V 

PROVIDER: S-EPMC5736353 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature