Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Cardiac Gene Expression Profiling in CryAB R120G Transgenic 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 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)

ORGANISM(S): Mus musculus

SUBMITTER: Brett Milash 

PROVIDER: E-GEOD-9924 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Rajasekaran Namakkal S NS   Firpo Matthew A MA   Milash Brett A BA   Weiss Robert B RB   Benjamin Ivor J IJ  

Physiological genomics 20080715 2


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 n  ...[more]

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