Down‐regulation of mitochondrial mRNAs in the <i>mdx</i> mouse model for Duchenne muscular dystrophy

Gannoun-Zaki, Laïla; Fournier-Bidoz, S; Cam, Ginette Le; Chambon, Christophe; Millasseau, Ph; Léger, J.; Dechesne, Claude J.

doi:10.1016/0014-5793(95)01225-4

Cited by 28 publications

(14 citation statements)

References 27 publications

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“…Downregulation of these genes, exclusively observed in mdx hindlimb muscles, indicated an impaired ATP synthesis and an alteration of metabolite supply for muscle activity. These findings served as a confirmation of observations by others that showed that the hindlimb (peripheral) muscles in DMD patients (2,11,49) and mdx mice (19,20,27) are affected by a generalized dysfunction of their energy machinery. The concomitant observation that the same gene set did not display differential expression in mdx diaphragm muscle indicated that the progressive and dramatic destruction of fibers from this muscle type possibly occurs without large perturbations of the metabolic machinery.…”

Section: Conclusion 2: Dystrophin Deficiency Causes Different Perturbsupporting

confidence: 88%

Global/temporal gene expression in diaphragm and hindlimb muscles of dystrophin-deficient (mdx) mice

Rouger

Cunff

Steenman

et al. 2002

American Journal of Physiology-Cell Physiology

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The mdx mouse is a model for human Duchenne muscular dystrophy (DMD), an X-linked degenerative disease of skeletal muscle tissue characterized by the absence of the dystrophin protein. The mdx mice display a much milder phenotype than DMD patients. After the first week of life when all mdx muscles evolve like muscles of young DMD patients, mdx hindlimb muscles substantially compensate for the lack of dystrophin, whereas mdx diaphragm muscle becomes progressively affected by the disease. We used cDNA microarrays to compare the expression profile of 1,082 genes, previously selected by a subtractive method, in control and mdx hindlimb and diaphragm muscles at 12 time points over the first year of the mouse life. We determined that 1) the dystrophin gene defect induced marked expression remodeling of 112 genes encoding proteins implicated in diverse muscle cell functions and 2) two-thirds of the observed transcriptomal anomalies differed between adult mdx hindlimb and diaphragm muscles. Our results showed that neither mdx diaphram muscle nor mdx hindlimb muscles evolve entirely like the human DMD muscles. This finding should be taken under consideration for the interpretation of future experiments using mdx mice as a model for therapeutic assays.

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Section: Conclusion 2: Dystrophin Deficiency Causes Different Perturbsupporting

confidence: 88%

Global/temporal gene expression in diaphragm and hindlimb muscles of dystrophin-deficient (mdx) mice

Rouger

Cunff

Steenman

et al. 2002

American Journal of Physiology-Cell Physiology

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“…Muscle dystrophy and other muscle diseases are often associated with decline in nuclear-encoded mitochondrial gene expression or mitochondrial dysfunction (Chen et al, 2000;Gannoun-Zaki et al, 1995;Kuznetsov et al, 1998). To determine whether the primary effect of the Ewg null mutation is on muscle degeneration with consequent mitochondrial defects or the reverse causality of a primary mitochondrial defect leading to muscle degeneration, a knockdown of Opa1-like was performed.…”

Section: Results (Supplementary Materialsmentioning

confidence: 99%

Drosophila Erect wing (Ewg) controls mitochondrial fusion during muscle growth and maintenance by regulation of the Opa1-like gene

Rai

Katti

Nongthomba

2013

Journal of Cell Science

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Mitochondrial biogenesis and morphological changes are associated with tissue-specific functional demand, but the factors and pathways that regulate these processes have not been completely identified. A lack of mitochondrial fusion has been implicated in various developmental and pathological defects. The spatiotemporal regulation of mitochondrial fusion in a tissue such as muscle is not well understood. Here, we show in Drosophila indirect flight muscles (IFMs) that the nuclear-encoded mitochondrial inner membrane fusion gene, Opa1-like, is regulated in a spatiotemporal fashion by the transcription factor/co-activator Erect wing (Ewg). In IFMs null for Ewg, mitochondria undergo mitophagy and/or autophagy accompanied by reduced mitochondrial functioning and muscle degeneration. By following the dynamics of mitochondrial growth and shape in IFMs, we found that mitochondria grow extensively and fuse during late pupal development to form the large tubular mitochondria. Our evidence shows that Ewg expression during early IFM development is sufficient to upregulate Opa1-like, which itself is a requisite for both late pupal mitochondrial fusion and muscle maintenance. Concomitantly, by knocking down Opa1-like during early muscle development, we show that it is important for mitochondrial fusion, muscle differentiation and muscle organization. However, knocking down Opa1-like, after the expression window of Ewg did not cause mitochondrial or muscle defects. This study identifies a mechanism by which mitochondrial fusion is regulated spatiotemporally by Ewg through Opa1-like during IFM differentiation and growth.

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“…The values Apt/Apo and Ant/Ano may be approximated as nearly constant values 1.57 and 1.38, respectively, independent of Apr or Anr (see Table 1) the progressive debilitating disorder of DMD. In addition, changes in gene expression in dystrophin-deficient skeletal muscles (Gannoun-Zaki et al 1995;Chen et al 2000;Tkatchenko et al 2001;Tseng et al 2002;Noguchi et al 2003;Nakayama et al 2004) are possibly due to oxidative DNA damage which would not be lethal lesions but mutagenic lesions. Our new technique for the assessment of oxidative stress in nuclear DNA in tissues would be applicable for the quantitative assay of other oxidative products of DNA bases (Wallace 2002;Bjelland and Seeberg 2003) if their specific antibodies are available.…”

Section: Discussionmentioning

confidence: 96%

A new technique for the quantitative assessment of 8-oxoguanine in nuclear DNA as a marker of oxidative stress. Application to dystrophin-deficient DMD skeletal muscles

Nakae

Stoward

Bespalov

et al. 2005

Histochem Cell Biol

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This is the first report on the development of an immunohistochemical technique, combined with quantitative image analysis, for the assessment of oxidative stress quantitatively in nuclear DNA in situ, and its application to measure DNA damage in Duchenne muscular dystrophic (DMD) muscles. Three sequential staining procedures for cell nuclei, a cell marker, and a product of oxidative DNA damage, 8-oxoguanine (8-oxoG), were performed. First, the nuclei in muscle sections were stained with Neutral Red followed by the capture of their images with an image analysis system used for absorbance measurements. Second, the same sections were then immunostained for laminin in basement membranes as the cell marker. Next, the sections were treated with 2 N HCl to remove the bound Neutral Red and to denature tissue DNA. Third, the sections were immunostained for 8-oxoG in DNA, using diaminobenzidine (DAB) to reveal the antibody complex. This was followed by capture of the images of the immunostained sections as previously. The absorbances at 451.2 nm of bound Neutral Red and DAB polymer oxides, the final product of 8-oxoG immunostaining, were measured in the same myonuclei in the sections. Analysis of these absorbances permitted indices of the 8-oxoG content, independent of the nuclear densities, to be determined in nuclear DNA in single myofibres and myosatellite cells surrounded by basement membranes. We found that the mean index for the myonuclei in biceps brachii muscles of 2- to 7-year-old patients was 14% higher than that in age-matched normal controls. This finding of the increased oxidative stress in the myonuclei in young DMD muscles agrees with the previous reports of increased oxidative stress in the cytoplasm in the DMD myofibres and myosatellite cells. The present technique for the quantitative assessment of oxidative stress in nuclear DNA in situ is applicable not only in biomedical research but also in the development of effective drugs for degenerative diseases related to oxidative stress.

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Down‐regulation of mitochondrial mRNAs in the mdx mouse model for Duchenne muscular dystrophy

Cited by 28 publications

References 27 publications

Global/temporal gene expression in diaphragm and hindlimb muscles of dystrophin-deficient (mdx) mice

Global/temporal gene expression in diaphragm and hindlimb muscles of dystrophin-deficient (mdx) mice

Drosophila Erect wing (Ewg) controls mitochondrial fusion during muscle growth and maintenance by regulation of the Opa1-like gene

A new technique for the quantitative assessment of 8-oxoguanine in nuclear DNA as a marker of oxidative stress. Application to dystrophin-deficient DMD skeletal muscles

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