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| Status |
Public on Dec 31, 2009 |
| Title |
SOCS-3 in muscle |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Aims/hypothesis Due to their ability to regulate various signalling pathways (cytokines, hormones, growth factors), the suppressor of cytokine signalling (SOCS) proteins are thought to be promising therapeutic targets for metabolic and inflammatory disorders. Hence, their role in vivo has to be precisely determined.
Methods We generated transgenic mice constitutively expressing SOCS-3 in skeletal muscle to define whether the sole expression of SOCS-3 is sufficient to induce metabolic disorders and whether SOCS-3 is implicated in physiological roles distinct from metabolism.
Results We demonstrate here that chronic expression of SOCS-3 in skeletal muscle leads to overweight in mice and worsening of high-fat diet-induced systemic insulin resistance. Counter intuitively, insulin sensitivity in muscle of transgenic mice appears to be unaltered. However, following constitutive SOCS-3 expression, several genes had deregulated expression, among them other members of the SOCS family. This could maintain the insulin signal into skeletal muscle. Interestingly, we found that SOCS-3 interacts with calcineurin, which has been implicated in muscle contractility. In SOCS-3 transgenic muscle, this leads to delocalisation of calcineurin to the fibre periphery. Relevant to this finding, SOCS-3 transgenic animals had dilatation of the sarcoplasmic reticulum associated with swollen mitochondria and decreased voluntary activity.
Conclusions/interpretation Our results show that constitutive SOCS-3 expression in skeletal muscle is not in itself sufficient to induce the establishment of metabolic disorders such as diabetes. In contrast, we reveal a novel role of SOCS-3, which appears to be important for muscle integrity and locomotor activity.
(Patricia Lebrun et al, Diabetologia, 2009)
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| Overall design |
Expression profile established on a MoGene platform (Affymetrix), using three replicate for the wild type (WT), and three replicates for the transgene (TG).
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| Contributor(s) |
Lebrun P, Moreilhon C, Lebrigand K, Barbry P, Van Obberghen E |
| Citation(s) |
19672574 |
| Submission date |
Jul 13, 2009 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Kevin Lebrigand |
| Organization name |
IPMC/CNRS
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| Lab |
Functional Genomics Platform of Nice-Sophia-Antipolis, France.
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| Street address |
660 route des lucioles
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| City |
Valbonne - Sophia-Antipolis |
| ZIP/Postal code |
06560 |
| Country |
France |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA119841 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE17063_RAW.tar |
25.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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