Fine structure of early degenerating myofibers in the tibialis anterior of young ‘MDX’ mouse

1988 ◽  
Vol 46 ◽  
pp. 322-323
Author(s):  
H.D. Geissinger ◽  
C.K. McDonald-Taylor
Keyword(s):  
Fine Structure ◽  
Muscle Regeneration ◽  
Tibialis Anterior ◽  
Genetic Defect ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Histopathological Changes ◽  
Electron Microscopic ◽  
Dystrophic Mouse ◽  
Preliminary Study

A new strain of mice, which had arisen by mutation from a dystrophic mouse colony was designated ‘mdx’, because the genetic defect, which manifests itself in brief periods of muscle destruction followed by episodes of muscle regeneration appears to be X-linked. Further studies of histopathological changes in muscle from ‘mdx’ mice at the light microscopic or electron microscopic levels have been published, but only one preliminary study has been on the tibialis anterior (TA) of ‘mdx’ mice less than four weeks old. Lesions in the ‘mdx’ mice vary between different muscles, and centronucleation of fibers in all muscles studied so far appears to be especially prominent in older mice. Lesions in young ‘mdx’ mice have not been studied extensively, and the results appear to be at variance with one another. The degenerative and regenerative aspects of the lesions in the TA of 23 to 26-day-old ‘mdx’ mice appear to vary quantitatively.

Hyperthyroidism impairs early repair in normal but not dystrophic mdx mouse tibialis anterior muscle. An in vivo study

1996 ◽  
Vol 74 (3) ◽  
pp. 315-324 ◽  
Author(s):  
A. N. Pernitsky ◽  
L. M. McIntosh ◽  
J. E. Anderson
Keyword(s):  
Muscle Regeneration ◽  
Tibialis Anterior ◽  
Mononuclear Cells ◽  
Strain Difference ◽  
Tibialis Anterior Muscle ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Cross Sectional ◽  
Fiber Damage

The effect of hyperthyroidism on muscle repair was examined in mdx and control mice injected with triiodothyronine (T3) for 4 weeks. On day 24 of treatment, the right tibialis anterior (TA) muscle was crush-injured; 3 days later, mice received intraperitoneal [3H]thymidine to label newly synthesized DNA. One day later, muscles from both limbs were removed to study the severity of dystrophy (uncrushed muscle) and the regeneration response (crushed muscle). In uncrushed TA muscle, the area of active dystrophy (fiber damage and infiltration as a proportion of muscle cross-sectional area) was reduced by half after T3 treatment. Uncrushed muscle fiber diameter was lower in T3-treated control muscles. In crushed muscles, the diameter of new myotubes was larger in mdx mice than in controls and was reduced after T3 treatment in control regenerating muscle. In the same muscles, developmental myosin heavy chain was present in new myotubes and in small numbers of mononuclear cells (possibly differentiating myoblasts) near new myotubes and surviving fibers. Myotube density in the regenerating muscles was not changed by T3 treatment, although the number of myotube nuclei per field was decreased in control and increased in mdx T3-treated mice. Results extend previous reports of T3 effects on dystrophy and the strain difference in muscle precursor cell (mpc) proliferation. The results also suggest the hypothesis that excess T3 affects muscle regeneration either by reducing mpc proliferation or by increasing mpc fusion early in regeneration in control and mdx muscle.Key words: hypothyroid, muscle regeneration, crush injury, proliferation, mdx mouse.

Muscle genome-wide expression profiling during disease evolution in mdx mice

2009 ◽  
Vol 37 (2) ◽  
pp. 119-132 ◽  
Author(s):  
Mario Marotta ◽  
Claudia Ruiz-Roig ◽  
Yaris Sarria ◽  
Jose Luis Peiro ◽  
Fatima Nuñez ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Genetic Defect ◽  
Strong Relationship ◽  
Pcr Analysis ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Matrix Remodeling ◽  
Disease Evolution ◽  
Genome Wide ◽  
Muscle Necrosis

Mdx mice show a milder phenotype than Duchenne patients despite bearing an analogous genetic defect. Our aim was to sort out genes, differentially expressed during the evolution of skeletal muscle mdx mouse disease, to elucidate the mechanisms by which these animals overcome the lack of dystrophin. Genome-wide microarray-based gene expression analysis was carried out at 3 wk and 1.5 and 3 mo of life. Candidate genes were selected by comparing: 1) mdx vs. controls at each point in time, and 2) mdx mice and 3) control mice among the three points in time. The first analysis showed a strong upregulation (96%) of inflammation-related genes and in >75% of genes related to cell adhesion, muscle structure/regeneration, and extracellular matrix remodeling during mdx disease evolution. Lgals3, Postn, Ctss, and Sln genes showed the strongest variations. The analysis performed among points in time demonstrated significant changes in Ecm1, Spon1, Thbs1, Csrp3, Myo10, Pde4b, and Adamts-5 exclusively during mdx mice lifespan. RT-PCR analysis of Postn, Sln, Ctss, Thbs1, Ecm1, and Adamts-5 expression from 3 wk to 9 mo, confirmed microarray data and demonstrated variations beyond 3 mo of age. A high-confidence functional network analysis demonstrated a strong relationship between them and showed two main subnetworks, having Dmd- Utrn- Myo10 and Adamts5- Thbs1- Spon1-Postn as principal nodes, which are functionally linked to Abca1, Actn4, Crebbp, Csrp3, Lama1, Lama3, Mical2, Mical3, Myf6, Pxn, and Sparc genes. Candidate genes may participate in the decline of muscle necrosis in mdx mice and could be considered potential therapeutic targets for Duchenne patients.

scholarly journals Clonal Isolation of Muscle-Derived Cells Capable of Enhancing Muscle Regeneration and Bone Healing

2000 ◽  
Vol 150 (5) ◽  
pp. 1085-1100 ◽  
Author(s):  
Joon Yung Lee ◽  
Zhuqing Qu-Petersen ◽  
Baohong Cao ◽  
Shigemi Kimura ◽  
Ron Jankowski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Bone Healing ◽  
Muscle Regeneration ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Hematopoietic Stem ◽  
Isolation And Characterization ◽  
Osteogenic Lineage

Several recent studies suggest the isolation of stem cells in skeletal muscle, but the functional properties of these muscle-derived stem cells is still unclear. In the present study, we report the purification of muscle-derived stem cells from the mdx mouse, an animal model for Duchenne muscular dystrophy. We show that enrichment of desmin+ cells using the preplate technique from mouse primary muscle cell culture also enriches a cell population expressing CD34 and Bcl-2. The CD34+ cells and Bcl-2+ cells were found to reside within the basal lamina, where satellite cells are normally found. Clonal isolation and characterization from this CD34+Bcl-2+ enriched population yielded a putative muscle-derived stem cell, mc13, that is capable of differentiating into both myogenic and osteogenic lineage in vitro and in vivo. The mc13 cells are c-kit and CD45 negative and express: desmin, c-met and MNF, three markers expressed in early myogenic progenitors; Flk-1, a mouse homologue of KDR recently identified in humans as a key marker in hematopoietic cells with stem cell-like characteristics; and Sca-1, a marker for both skeletal muscle and hematopoietic stem cells. Intramuscular, and more importantly, intravenous injection of mc13 cells result in muscle regeneration and partial restoration of dystrophin in mdx mice. Transplantation of mc13 cells engineered to secrete osteogenic protein differentiate in osteogenic lineage and accelerate healing of a skull defect in SCID mice. Taken together, these results suggest the isolation of a population of muscle-derived stem cells capable of improving both muscle regeneration and bone healing.

MDX mouse myopathy II: Degenerative changes in centronucleated fibers from mice of different ages

1989 ◽  
Vol 47 ◽  
pp. 1072-1073
Author(s):  
H.D. Geissinger ◽  
P.A. Rhodes
Keyword(s):  
Tibialis Anterior ◽  
Degenerative Changes ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Pathological Changes ◽  
Previous Episode ◽  
The Third ◽  
Different Ages ◽  
Prominent Nucleolus

Ultrastructural features of centronucleated (regenerating) fibers of ‘mdx’ mice have been reported in three different papers and in all three, different features of these fibers were described in some detail. Thus, in one paper “abortive attempts at regeneration” in very young fibers, in another early degeneration of regenerating fibers and in the third paper “healthy” regenerating fibers, as well as degenerating myotubes were shown. We show the probable pathogenesis of degeneration of centronucleated fibers in ‘mdx’ mice.METHODS: Tibialis anterior muscles from 22-, 25-, 41-, 61- and 99-days-old C57BL/10ScSn/MDX mice were pinned on corkboard in a relaxed state, prefixed for 30 minutes in glutaraldehyde followed by routine processing for TEM.RESULTS: In a 41-days-old ‘mdx’ mouse a fiber which had apparently fully regenerated from a previous episode of necrosis is shown in FIG. 1. Since there are no pathological changes in this fiber, it will serve as a control. The nucleus has a fairly prominent nucleolus and there are no lesions in the myofibrils and the rest of the sarcoplasm.

MDX mouse myopathy I: Presence or absence of sarcolemmal lesions in tibialis anterior muscles from mice of different ages

1989 ◽  
Vol 47 ◽  
pp. 1070-1071
Author(s):  
H.D. Geissinger ◽  
L.D. Rhodes
Keyword(s):  
Animal Model ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Tibialis Anterior ◽  
Extensor Digitorum Longus ◽  
Morphological Analysis ◽  
Control Mouse ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Recent Interest

Since the ‘mdx’ mouse appears to have the same basic defect as sufferers of human Duchenne Muscular Dystrophy (DMD), much recent interest in this possible animal model for the human disease has been generated. Perforations in the sarcolemma have been reported recently in the necrotic tibialis anterior (TA) of 35-days-old and the extensor digitorum longus muscles of 39-days-old ‘mdx’ mice. It is the purpose of this communication to find out if these lesions occur not only in necrotic, but also in unaffected, or in centronucleated fibers of the TA of mice which are younger than 35, or older than 39 days.METHODS: TA from 22-, 25-, 41-, 61- and 99-days-old C57BL/10ScSn/MDX and C57BL/lOScSn control mice were pinned on corkboard in a relaxed state, prefixed for 30 minutes in 2.5% glutaraldehyde followed by routine processing for TEM. Appropriate micrographs were evaluated for a more detailed morphological analysis of the sarcolemma (SL) and the basal lamina (BL).RESULTS: It should be stated beforehand that in all muscles examined the BL appeared to be intact. In the muscles of a 25-days-old control mouse the SL appeared quite intact (FIG. 1). In contrast to this small perforations or large tears in the SL could be seen in otherwise unaffected muscles of 22- (FIG. 2), 25- and 41-days-old ‘mdx’ mice, as well as in necrotic and regenerating fibers of mice from these ages.

scholarly journals Profiling of Age-Related Changes in theTibialis AnteriorMuscle Proteome of the mdx Mouse Model of Dystrophinopathy

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Steven Carberry ◽  
Margit Zweyer ◽  
Dieter Swandulla ◽  
Kay Ohlendieck
Keyword(s):  
Muscular Dystrophy ◽  
Tibialis Anterior ◽  
Large Scale ◽  
Small Heat Shock Protein ◽  
Dystrophin Gene ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Global Changes ◽  
Altered Expression ◽  
Age Related

X-linked muscular dystrophy is a highly progressive disease of childhood and characterized by primary genetic abnormalities in the dystrophin gene. Senescent mdx specimens were used for a large-scale survey of potential age-related alterations in the dystrophic phenotype, because the established mdx animal model of dystrophinopathy exhibits progressive deterioration of muscle tissue with age. Since the mdxtibialis anteriormuscle is a frequently used model system in muscular dystrophy research, we employed this particular muscle to determine global changes in the dystrophic skeletal muscle proteome. The comparison of mdx mice aged 8 weeks versus 22 months by mass-spectrometry-based proteomics revealed altered expression levels in 8 distinct protein species. Increased levels were shown for carbonic anhydrase, aldolase, and electron transferring flavoprotein, while the expressions of pyruvate kinase, myosin, tropomyosin, and the small heat shock protein Hsp27 were found to be reduced in aged muscle. Immunoblotting confirmed age-dependent changes in the density of key muscle proteins in mdx muscle. Thus, segmental necrosis in mdxtibialis anteriormuscle appears to trigger age-related protein perturbations due to dystrophin deficiency. The identification of novel indicators of progressive muscular dystrophy might be useful for the establishment of a muscle subtype-specific biomarker signature of dystrophinopathy.

Contractile properties and susceptibility to exercise-induced damage of normal and mdx mouse tibialis anterior muscle

1992 ◽  
Vol 82 (2) ◽  
pp. 227-236 ◽  
Author(s):  
P. Sacco ◽  
D. A. Jones ◽  
J. R. T. Dick ◽  
G. Vrbová
Keyword(s):  
Muscle Damage ◽  
Tibialis Anterior ◽  
Time Course ◽  
Tibialis Anterior Muscle ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Force Frequency ◽  
Maximal Force ◽  
Exercise Induced ◽  
40 Hz

1. The functional properties of tibialis anterior muscles of normal adult (C57BL/10) and age-matched dystrophin-deficient (C57BL/10 mdx) mice have been investigated in situ. Comparisons were made between tibialis anterior muscle strength, rates of force development and relaxation, force-frequency responses and fatiguability. Subjecting mdx and C57 muscles to a regimen of eccentric exercise allowed the hypothesis to be tested that dystrophin-deficient muscles are more susceptible to exercise-induced muscle damage. 2. mdx muscles were, on average, 30% stronger than C57 muscles and almost 80% heavier, but both had similar muscle lengths. Thus, although mdx muscles were stronger in absolute terms, their estimated force per unit cross-sectional area was significantly less than that of C57 muscles. 3. The force-frequency relationships of C57 and mdx muscles differed in that whilst, at 40 Hz, the former developed 70% of the force developed at 100 Hz, the latter developed only 55% of the maximal force. Twitch force was normal in mdx muscles, but contraction time was shortened, and the consequent reduction in fusion frequency probably explains the force-frequency differences observed between the two groups. 4. mdx muscles were less fatiguable than normal muscles when stimulated repeatedly at a frequency of 40 Hz. It is possible that the lower relative force at 40 Hz in mdx muscles entailed a lower energy demand and thus a slower rate of fatigue than seen in normal muscles. 5. Eccentrically exercised C57 muscles showed a large loss of maximal force for up to 12 days after exercise. Maximal force loss occurred 3 days after exercise (55% of non-exercised tibialis anterior muscle), which also corresponded with the period of greatest fibre necrosis. C57 muscles showed a significantly reduced 40 Hz/100 Hz force-frequency ratio at 1 and 3 days after exercise. This was primarily due to a reduced twitch amplitude rather than to a change in the time course of the twitch. It is unlikely, therefore, that the altered contractile characteristics of mdx muscle were a result of the presence of damaged but otherwise normal fibres. 6. C57 and mdx tibialis anterior muscles displayed similar degrees of force loss after exercise. Furthermore, the rate of recovery after the nadir of force loss was very similar for the two groups. By 12 days after exercise, force recovered to 76% and 80% of control in C57 and mdx muscles, respectively. Our findings do not support the hypothesis that dystrophin-deficient muscle is more susceptible to exercise-induced muscle damage.

Regenerating myofibers in tibialis anterior muscles of young ‘MDX’ mice

1987 ◽  
Vol 45 ◽  
pp. 726-727
Author(s):  
H. D. Geissinge ◽  
L.D. Rhodes
Keyword(s):  
Muscular Dystrophy ◽  
Mouse Model ◽  
Tibialis Anterior ◽  
Physiological Activity ◽  
Mdx Mice ◽  
Mode Of Inheritance

A recently discovered mouse model (‘mdx’) for muscular dystrophy in man may be of considerable interest, since the disease in ‘mdx’ mice is inherited by the same mode of inheritance (X-linked) as the human Duchenne (DMD) muscular dystrophy. Unlike DMD, which results in a situation in which the continual muscle destruction cannot keep up with abortive regenerative attempts of the musculature, and the sufferers of the disease die early, the disease in ‘mdx’ mice appears to be transient, and the mice do not die as a result of it. In fact, it has been reported that the severely damaged Tibialis anterior (TA) muscles of ‘mdx’ mice seem to display exceptionally good regenerative powers at 4-6 weeks, so much so, that these muscles are able to regenerate spontaneously up to their previous levels of physiological activity.

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

2002 ◽  
Vol 283 (3) ◽  
pp. C773-C784 ◽  
Author(s):  
Karl Rouger ◽  
Martine Le Cunff ◽  
Marja Steenman ◽  
Marie-Claude Potier ◽  
Nathalie Gibelin ◽  
...  
Keyword(s):  
Dystrophin Gene ◽  
Diaphragm Muscle ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
First Year ◽  
Temporal Gene Expression ◽  
Cell Functions ◽  
Hindlimb Muscles ◽  
Genes Encoding ◽  
Dystrophin Protein

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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