Project description:We created mice, which are deficient for Myc specifically in cardiac myocytes by crossing crossed Myc-floxed mice (Mycfl/fl) and MLC-2VCre/+ mice. Serial analysis of earlier stages of gestation revealed that Myc-deficient mice died prematurely at E13.5-14.5. Morphological analyses of E13.5 Myc-null embryos showed normal ventricular size and structure; however, decreased cardiac myocyte proliferation and increased apoptosis was observed. BrdU incorporation rates were also decreased significantly in Myc-null myocardium. Myc-null mice displayed a 3.67-fold increase in apoptotic cardiomyocytes by TUNEL assay. We examined global gene expression using oligonucleotide microarrays. Numerous genes involved in mitochondrial death pathways were dysregulated including Bnip3L and Birc2. Keywords: wildtype vs Myc-null
Project description: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)
Project description:We created mice, which are deficient for Myc specifically in cardiac myocytes by crossing crossed Myc-floxed mice (Mycfl/fl) and MLC-2VCre/+ mice. Serial analysis of earlier stages of gestation revealed that Myc-deficient mice died prematurely at E13.5-14.5. Morphological analyses of E13.5 Myc-null embryos showed normal ventricular size and structure; however, decreased cardiac myocyte proliferation and increased apoptosis was observed. BrdU incorporation rates were also decreased significantly in Myc-null myocardium. Myc-null mice displayed a 3.67-fold increase in apoptotic cardiomyocytes by TUNEL assay. We examined global gene expression using oligonucleotide microarrays. Numerous genes involved in mitochondrial death pathways were dysregulated including Bnip3L and Birc2. Hearts were taken from wide type and Myc-null Mouse embryos at E13.5 under the dissecting scope. Cardiac myocyte RNA was isolated using TRIZOL®Reagent Total RNA (100 ng) was hybridized to the Sentrix® MouseRef-8 Expression BeadChip that contains probes for ~24,000 transcripts. GeneChips were scanned using the Hewlett-Packard GeneArray Scanner G2500A. The data were analyzed with Illumina Inc. BeadStudio version 1.5.0.34 and normalized by rank invariant method.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
Project description:Gene expression profiling of wildtype vs. transgenic mice expressing the cardiac specific genetically encoded FRET biosensor Epac1-PLN