Evolution of pathological changes in the gastrocnemius of the mdx mice correlate with utrophin and β-dystroglycan expression
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ID: 114155
2004
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Abstract
Utrophin can function in muscle as a substitute for dystrophin and its over-expression has been used successfully to ameliorate mdx muscle pathology. Despite of this fact, there are no detailed studies on the expression of endogenous skeletal muscle utrophin- and dystrophin-associated glycoproteins throughout the life span of mdx mice. We have monitored, sequentially, the expression of matrix metalloproteinase-9 (MMP-9), myosin heavy chain, utrophin and β-dystroglycan, as well as the mRNA expression of utrophin and of structurally related proteins, in mdx and control mice. We found an inverse relationship between concentration of muscle utrophin and abundance of groups of degenerative-regenerative fibers and of MMP-9 expression. There was also temporal correlation between the decline of utrophin at 15 days of age and the onset of muscle necrosis. Conversely, reappearance of utrophin, with a peak around 2 months of age, was followed by a progressive decline of necrosis. A lineal correlation between utrophin and β-dystroglycan levels, not seen in controls, indicates that improvement of mdx is due to utrophin binding to dystrophin-associated glycoproteins. Utrophin and other structurally related protein transcripts were not up-regulated, suggesting a post-transcriptional regulation for utrophin in skeletal muscle.
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roma2004actaevolution
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| Authors | Josep Roma;Francina Munell;Arnau Fargas;Manuel Roig;Josep Roma;Francina Munell;Arnau Fargas;Manuel Roig; |
| Journal | acta neuropathologica |
| Year | 2004 |
| DOI |
doi:10.1007/s00401-004-0908-1
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