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Series GSE124394 Query DataSets for GSE124394
Status Public on Mar 12, 2019
Title Role of p110a subunit of PI3-kinase in skeletal muscle mitochondria
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Skeletal muscle insulin resistance, decreased phosphatidylinositol 3-kinase (PI3K) activation and altered mitochondrial function are hallmarks of type 2 diabetes. We created mice with a muscle-specific knockout of p110α or p110β, the two major catalytic subunits of PI3K. We find that mice with muscle-specific knockout of p110α, but not p110β, display impaired muscle insulin signaling and reduced muscle size due to enhanced proteasomal and autophagic activity. Despite insulin resistance and muscle atrophy, M-p110αKO mice show decreased serum myostatin, increased mitochondrial mass, increased mitochondrial fusion visualized by intravital microscopy, and increased PGC1α expression, especially PCG1α2 and PCG1α3. This leads to enhanced mitochondrial oxidative capacity, striking increases in muscle NADH content, and higher muscle free radical release measured in vivo using pMitoTimer reporter. Thus, p110α is the dominant catalytic isoform of PI3K in muscle in control of insulin sensitivity and muscle mass, and has a unique role in mitochondrial homeostasis in skeletal muscle.
Overall design All studies were performed in male mice on C57BL/6J background. Muscle-specific p110alpha or p11beta knockout mice were generated by crossing mice carrying the Cre recombinase gene driven by the human alpha-skeletal actin (HSA) promoter (Jackson Laboratories Stock Number: 006149) with mice carrying either floxed p110alpha or p110beta alleles in which exon 1 of p110alpha or exon 2 of p110bet was flanked with loxP sites. Skeletal muscle from 2-3-month-old male mice was harvested and RNA was extracted using Trizol. Gene expression profiling was performed using NEBNext mRNA Sample Prep Master Mix kit (NEB) by BioPolymers Facility at Harvard Medical School. Reads were aligned to the mouse genome (GRCm38) using STAR aligner and counted with Subread featureCounts.
Contributor(s) Li ME, Kahn CR
Citation(s) 31363081
Submission date Dec 26, 2018
Last update date Aug 07, 2019
Contact name Hui Pan
Organization name Joslin Diabetes Center
Department Bioinformatics and Biostatistics Core
Street address 1 Joslin Place
City Boston
ZIP/Postal code 02215
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (29)
GSM3531643 1 Fed.p110alpha.WT
GSM3531644 2 Fed.p110alpha.WT
GSM3531645 3 Fed.p110alpha.WT
BioProject PRJNA511896
SRA SRP174500

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Supplementary file Size Download File type/resource
GSE124394_counts_table.csv.gz 952.9 Kb (ftp)(http) CSV
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