Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse extraocular and hindlimb muscle to determine gene expression changes in extraocular and hindlimb (gastrocnemius/soleus) of mdx (dystrophin-deficient) mice at postnatal day 56

ABSTRACT: Determination of gene expression changes in extraocular and hindlimb (gastrocnemius/soleus) of mdx (dystrophin-deficient) mice at postnatal day 56. 5 independent replicates/muscle group/strain.

ORGANISM(S): Mus musculus

SUBMITTER: Henry Kaminski

PROVIDER: E-GEOD-1472 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A chronic inflammatory response dominates the skeletal muscle molecular signature in dystrophin-deficient mdx mice.

Porter John D JD Khanna Sangeeta S Kaminski Henry J HJ Rao J Sunil JS Merriam Anita P AP Richmonds Chelliah R CR Leahy Patrick P Li Jingjin J Guo Wei W Andrade Francisco H FH

Human molecular genetics 20020201 3

Mutations in dystrophin cause Duchenne muscular dystrophy (DMD), but absent dystrophin does not invariably cause necrosis in all muscles, life stages and species. Using DNA microarray, we established a molecular signature of dystrophinopathy in the mdx mouse, with evidence that secondary mechanisms are key contributors to pathogenesis. We used variability controls, adequate replicates and stringent analytic tools, including significance analysis of microarrays to estimate and manage false positi ...[more]

PMID: 11823445

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Project description:In this study, in order to minimize the genetic variability of muscle samples we have used two approaches. First, we have analyzed the gene expression profile from a single skeletal muscle, the medial gastrocnemius (MG), and not from a pool of different muscles which could have different expression profiles. Second, we have performed the temporal gene expression profiling by extracting the MG muscles of the same individual from the both legs at two different times to minimize the inter-individual genetic variability. The MG muscle represent an excellent candidate for biopsy due to its easy accessible by surgery and also because its biopsy is well tolerated by the animals allowing us to perform another later biopsy in the other leg to obtain two MG samples of the same individual at two different times. Moreover, MG muscle is composed of approximately 20-30% type I (red) fibers and 70-80% type II (white) fibers {Ariano MA, 1973}, {Simard C, 1988}, {Zhan WZ, 1992} and therefore is more representative of skeletal muscle tissue in general than a muscle composed exclusively by red or white fibers. The transcript expression profiles in MG muscles from mdx and wild-type mice were analyzed at 3 weeks, 1.5 months and 3 months of life by using the 430 2.0 gene chips from Affymetrix (n=3 for each condition). The differentially expressed transcripts which showed differences ?1.5-fold were obtained by performing three different comparisons: 1) genes differentially expressed in mdx compared with controls at each point in time (additional file 1); 2) temporal analysis of the genes differentially expressed in mdx mice between the three points in time also compared with the variations in control mice (additional file 2); and 3) temporal analysis of the genes differentially expressed in control mice between the three points in time also compared with the variations in mdx mice (additional file 3). The first comparison that we performed, by comparing the gene expression between mdx and control mice at every point in time, was similar to that performed in previous longitudinal studies {Porter JD, 2003}, {Rouger K, 2002}, {Turk R, 2005}. However, the other two comparisons were directed to elucidate the genes that are varying throughout the period of time analyzed in every mice strain, and therefore we obtained on the one hand the genes that vary in mdx mice but not in wild-type, and on the other hand the genes that vary in control animals but remain unchanged in mdx mice between the times analyzed. To present the results in a more comprehensive form, all the genes were classified in seven different categories: Cell adhesion & extracellular matrix; Proteolysis; Muscle structure & regeneration; Inflammation & immune response; Cell signaling & cell communication; Metabolism; and Others/unknown. The resulting genes from our study were classified in their functional categories using information from Affymetrix (www.affymetrix.com) and from the Gene Ontology database accessible in the Jackson Laboratory Mouse Genome Informatics website (www.informatics.jax.org).

Dataset Information

Transcription profiling of mouse extraocular and hindlimb muscle to determine gene expression changes in extraocular and hindlimb (gastrocnemius/soleus) of mdx (dystrophin-deficient) mice at postnatal day 56

Publications

A chronic inflammatory response dominates the skeletal muscle molecular signature in dystrophin-deficient mdx mice.

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