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Series GSE14512 Query DataSets for GSE14512
Status Public on Apr 01, 2013
Title Muscle Ring Finger 1 (MuRF1) and MuRF2 are Necessary but Functionally Redundant During Developmental Cardiac Growth and Regulate E2F1-Mediated Gene Expression In Vivo
Organism Mus musculus
Experiment type Expression profiling by array
Summary Muscle ring finger (MuRF) proteins have been implicated in the transmission of mechanical forces to nuclear cell signaling pathways through their association with the sarcomere. We recently reported that MuRF1, but not MuRF2, regulated pathologic cardiac hypertrophy in vivo. This was surprising since MuRF1 and MuRF2 interact redundantly with sarcomeric proteins in yeast two hybrid studies, and form both homo- and hetero-dimers with each other. To determine if MuRF1 and MuRF2 were functionally redundant during development, we created mice lacking either 3 or 4 of the MuRF1 and MuRF2 alleles and compared them functionally. Surprisingly, only mice missing all four MuRF1 and MuRF2 alleles (MuRF1-/-//MuRF2-/-) developed a spontaneous hypertrophic cardiomyopathy - mice that were null for one of the genes, but heterozygous for the other (i.e. MuRF1-/-//MuRF2+/- or MuRF1+/-//MuRF2-/-) were phenotypically identical to wild type mice. Electron microscopy of the hearts of MuRF1-/-//MuRF2-/-(MuRF1/MuRF2 DN) mice identified altered Z disc and M line architecture, and a distinct swelling of mitochondria. MuRF1-/-//MuRF2-/- mouse hearts displayed increased expression of genes associated with fetal cardiac metabolism, including smooth muscle actin and b myosin heavy chain, suggesting that the cardiac hypertrophy seen in these mice was associated with a reversion to a fetal gene program. Despite our prediction that we would also see an increase in glucose compared to fatty acid oxidation (another trait of fetal cardiac metabolism) we saw that MuRF1-/-//MuRF2-/- heart homogenates oxidized significantly less glucose compared to controls, suggesting an important role for MuRF1 and MuRF2 in the regulation of glucose metabolism in vivo. This study identifies a previously unreported redundancy in the function of MuRF proteins in normal cardiac development.

Keywords: Genetic modification.
Overall design Four strain-matched groups of 12 week old mice were investigated: 1) MuRF1 -/- MuRF2 -/-; 2) MuRF1 +/+ MuRF2 +/+; 3) MuRF1 -/- MuRF2 +/-; 4) MuRF1 +/- MuRF2 -/-. Biological replicates: 4 WT, 4 MuRF1 -/- // MuRF2 -/-, 4 MuRF1 +/- //MuRF2 -/-, 4 MuRF1 -/- // MuRF2 +/-. Hearts harvested. One replicate per array.
Contributor(s) Willis MS, Wadosky KM, Rodriguez J, Schisler JC, Lockyer P, Hilliard EG, Glass DJ, Patterson C
Citation(s) 23512667
Submission date Jan 22, 2009
Last update date Jan 12, 2017
Contact name Monte Shaw Willis
Phone 919-843-1938
Organization name University of North Carolina
Department Pathology & Laboratory Medicine
Street address 103 Mason Farm Road, MBRB 2340B
City Chapel Hill
State/province NC
ZIP/Postal code 27599-7525
Country USA
Platforms (1)
GPL7202 Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version)
Samples (16)
GSM362602 MuRF1 -/- // MuRF2 -/-: Biological replicate 1.
GSM362603 MuRF1 -/- // MuRF2 -/-: Biological replicate 2.
GSM362604 MuRF1 +/+ // MuRF2 +/+: Biological replicate 1.
BioProject PRJNA111657

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Supplementary file Size Download File type/resource
GSE14512_RAW.tar 211.7 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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