Global expression profiling identifies a novel biosignature for protein aggregation R120GCryAB cardiomyopathy in mice.

ABSTRACT: Protein aggregation cardiomyopathy is a life-threatening manifestation of a multisystem disorder caused by the exchange mutation in the gene encoding the human small heat shock protein alphaB-crystallin (hR120GCryAB). Genetic studies in mice have established cardiac hR120GCryAB expression causes increased activity of glucose 6-phosphate dehydrogenase (G6PD) and "reductive stress" (Rajasekaran et al., Cell 130: 427-439, 2007). However, the initiating molecular events in the pathogenesis of this novel toxic gain-of-function mechanism remain poorly defined. In an integrated systems approach using gene expression profiling, we identified a "biosignature," whose features can be validated to predict the onset, rate of progression, and clinical outcome of R120GCryAB cardiomyopathy. At the 3 mo di

SUBMITTER: Rajasekaran NS 

PROVIDER: S-EPMC2575954 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature