Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Dysregulated gene expression in Mef2a knockout mice subjected to cardiotoxin-induced muscle injury

ABSTRACT: We identified genes expressed in mouse skeletal muscle, during the process of muscle regeneration after injury, which are dysregulated in the absence of Mef2a expression. MEF2A is a member of the evolutionarily conserved MEF2 transcription factor family which has known roles in cardiac muscle development and function, but is not well studied in skeletal muscle. We performed a comparison of gene expression profiles in wild type and MEF2A knockout tibialis anterior muscle, seven days post-injury with cardiotoxin. The results indicated that a variety of genes expressed during muscle regeneration, predominantly microRNAs in the Gtl2-Dio3 locus, are dysregulated by the loss of MEF2A expression. Skeletal muscle RNA used in the present study included the following two sample groups: (WT) pooled total RNA from tibialis anterior muscle taken from 5 wild type mice at seven days post-injury with 10uM cardiotoxin; (KO) pooled total RNA from tibialis anterior muscle taken from 5 Mef2a knockout mice at seven days post-injury with 10uM cardiotoxin. All mice were between 2-4 months of age. Both male and female mice were used.

ORGANISM(S): Mus musculus

SUBMITTER: Frank Naya

PROVIDER: E-GEOD-41871 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

MEF2A regulates the Gtl2-Dio3 microRNA mega-cluster to modulate WNT signaling in skeletal muscle regeneration.

Snyder Christine M CM Rice Amanda L AL Estrella Nelsa L NL Held Aaron A Kandarian Susan C SC Naya Francisco J FJ

Development (Cambridge, England) 20121115 1

Understanding the molecular mechanisms of skeletal muscle regeneration is crucial to exploiting this pathway for use in tissue repair. Our data demonstrate that the MEF2A transcription factor plays an essential role in skeletal muscle regeneration in adult mice. Injured Mef2a knockout mice display widespread necrosis and impaired myofiber formation. MEF2A controls this process through its direct regulation of the largest known mammalian microRNA (miRNA) cluster, the Gtl2-Dio3 locus. A subset of ...[more]

PMID: 23154418

Similar Datasets

Project description:Mice were subjected to 50 eccentric contractions (EC) or 50 isometric contractions (IC) using a non-invasive model, and then sacrificed 48 hours later. RNA from the tibialis anterior of 4 animals were pooled and then split into two groups for hybridization onto two separate Affymetrix MGU74Av2 chips. Control samples were contralateral to the exercised legs, and were only subjected to enough contractions to measure isometric torque. Eccentric contractions (ECs), in which a muscle is forced to lengthen while activated, result in muscle injury and, eventually, muscle strengthening and prevention of further injury. Although the mechanical basis of eccentric contraction-induced injury has been studied in detail, muscle's biological response is less well characterized. This study presents the development of a minimally-invasive model of EC injury in the mouse, follows the time course of torque recovery after an injurious bout of ECs, and uses Affymetrix microarrays to compare the gene expression profile 48 hours after ECs to both isometrically stimulated muscles and contralateral muscles. Torque dropped by about 55% immediately after the exercise bout, and recovered to initial levels 7 days later. 36 known genes were upregulated after ECs compared to contralateral and isometrically stimulated muscles, including five muscle specific genes: muscle LIM protein (MLP), Muscle Ankyrin Repeat Proteins (MARP 1 and 2; also known as cardiac ankyrin repeat protein and Arpp/Ankrd2, respectively), Xin, and Myosin Binding Protein H. The time courses of MLP and MARP expression after the injury bout (determined by quantitative real-time polymerase chain reaction) indicate that these genes are rapidly induced, reaching a peak expression level of 6-11 times contralateral values 12-24 hours after the EC bout and returning to baseline within 72 hours. Very little gene induction was seen after either isometric activation or passive stretch, indicating that the MLP and MARP genes may play an important and specific role in the biological response of muscle to EC-induced injury. Keywords = mouse tibialis anterior eccentric contraction muscle

Dataset Information

Dysregulated gene expression in Mef2a knockout mice subjected to cardiotoxin-induced muscle injury

Publications

MEF2A regulates the Gtl2-Dio3 microRNA mega-cluster to modulate WNT signaling in skeletal muscle regeneration.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets