Cardiac Gene Expression Profiling in CryAB R120G Transgenic Mice

Protein aggregation cardiomyopathy is a life-threatening manifestation of a multisystem disorder caused by the exchange mutation in the gene encoding the human small HSP ?B-crystallin (hR120GCryAB). Genetic studies in mice have established cardiac hR120GCryAB expression causes increased activity of glucose 6-phosphate dehydrogenase (G6PD) and 'reductive stress' (Rajasekeran et al., Cell. 2007;130(3):401-2). 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. Keywords: time-course, genetic modification, disease state analysis 34 total samples were analyzed in in-house spotted microarrays (NIA mouse clone set), 2 time points (3 and 6 month old mice), 3 mouse strains (nontransgenic, human CryAB wild type transgenic, human R120G CryAB transgenic), 4-7 replicates per group, reference standard design (Stratagene Universal Mouse Reference RNA)