Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0016719 (
Friedreich's ataxia
)
2,098
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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 transcriptomic dysregulation even after substantial motor dysfunction and pathology were observed. This model will be of broad utility in therapeutic development and in refining our understanding of the relative contribution of reversible cellular dysfunction at different stages in disease.
...
PMID:Inducible and reversible phenotypes in a novel mouse model of Friedreich's Ataxia. 2925 45
