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Muscle Clock knock out mice metabolic changes (iMSBmal1-Exp1)

ABSTRACT: My lab studies the function of the molecular clocks in skeletal muscle. We have an inducible genetic mouse model (C57Bl6 background) in which we knock out the core clock gene, Bmal1, only in adult skeletal muscle after treatment with tamoxifen. We have found that the mice maintain body mass but lose fat mass at 10 weeks after loss of Bmal1. We have done expression profiling on the skeletal muscles and gene expression changes (insulin signaling, CHO metabolism, fat metabolism) suggest significant changes in substrate metabolism. To analyze TCA, CHO metabolites we have collected gastrocnemius muscles from these mice following instructions from Dr. Burant. Mice were anaesthetized with isoflurane, the gastrocnemius muscle dissected and flash frozen with tongs cooled with liquid N2. They have been stored in cryovials in our -80 freezer for 2 months.

ORGANISM(S): Mouse Mus Musculus

TISSUE(S): Muscle

SUBMITTER: Maureen Kachman

PROVIDER: ST000313 | MetabolomicsWorkbench | Thu Mar 26 00:00:00 GMT 2015

REPOSITORIES: MetabolomicsWorkbench

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Project description:Introduction: The mouse skeletal muscle is composed of four distinct fiber types that differ in contractile function, number of mitochondria and metabolism. Every muscle group has a specific composition and distribution of the four fiber types. Until now, three genes (CnA, PGC1α and PPARδ) are identified that are involved in the generation of more oxidative muscle types. In the present study we searched for novel genes that are involved in specifying different muscle types. Methods: Gastrocnemius and quadriceps muscles were dissected from 20-week old C57BL/6J mice. Gene expression profiles were compared at the level of the whole-transcriptome. The diet-sensitivity of genes differentially expressed between muscle types was explored by comparing mice fed a low fat diet with mice fed a high fat diet. Results: We identified 162 differentially expressed genes in the gastrocnemius as compared with the quadriceps. Genes with the strongest regulations were markers for oxidative fiber types, Hoxd8, Hoxd9 and Hoxd10 and others involved in embryogenesis. Additionally, diet did not influence the expression levels of genes specifying muscle types. Finally, when extrapolating our data to the soleus we could not find a corresponding gene expression pattern between Hoxd8, Hoxd9 and any of the fiber-type specific markers. However, based on these gene expression patterns we could distinguish the gastrocnemius, quadriceps and soleus from each other. Conclusion: Hoxd genes and genes that are markers for the different fiber types specify muscle type in a diet-independent way The aim of the present study was to find novel genes that may play a role in specifying muscle types. Therefore we compared gene expression profiles of the gastrocnemius with the quadriceps at the level of the whole-transcriptome. Functional implications were assessed by the analyses of predefined gene sets based on Gene Ontology, biochemical, metabolic and signaling pathways. muscle-type comparison

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Muscle Clock knock out mice metabolic changes (iMSBmal1-Exp1)

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