Temporal changes in magnetic resonance imaging in the mdx mouse
30
Citation
34
Reference
10
Related Paper
Citation Trend
Abstract:
Abstract Background Duchenne muscular dystrophy (DMD) is characterized clinically by severe, progressive loss of skeletal muscle. The phenotype is much less severe in the mdx mouse model of DMD than that seen in patients with DMD. However, a “critical period” has been described for the mdx mouse, during which there is a peak in muscle weakness and degeneration/regeneration between the 2 nd and 5 th weeks of life. A number of studies have employed small animal magnetic resonance imaging (MRI) to examine skeletal muscle in various dystrophic models, but such studies represent a snapshot in time rather than a longitudinal view. Results The in vivo cross-sectional T 2 -weighted image of the healthy (wild type, WT) muscles is homogeneously dark and this homogeneity does not change with time, as there is no disease. We, and others, have shown marked changes in MRI in dystrophic muscle, with multiple, unevenly distributed focal hyperintensities throughout the bulk of the muscles. Here we monitored an mdx mouse using MRI from 5 to 80 weeks of age. Temporal MRI scans show an increase in heterogeneity shortly after the critical period, at 9 and 13 weeks of age, with a decrease in heterogeneity thereafter. The 4.3-fold increase in percent heterogeneity at week 9 and 13 is consistent with the notion of an early critical period described for mdx mice. Conclusions Age is a significant variable in quantitative MR studies of the mdx mouse. The mdx mouse is typically studied during the critical period, at a time that most closely mimics the DMD pathology, but the preliminary findings here, albeit based on imaging only one mdx mouse over time, suggest that the changes in MRI can occur shortly after this period, when the muscles are still recovering.Keywords:
mdx mouse
Utrophin
ITGA7
mdx mouse
Cite
Citations (50)
ABSTRACT The mdx mouse has been used as an animal model for human Duchenne muscular dystrophy (DMD). Unlike DMD, skeletal muscles of mdx mice undergo successful regeneration and do not show extensive fibrosis and functional impairment. Growth factors have been proposed to be involved in muscle growth and regeneration. We compared mitogenic activity for skeletal myoblasts released after injury in mdx and control mice, using crushed muscle extract (CME) as a model system. We found that CMEs from normal and mdx mice contained similar mitogenic activities per microgram protein, and produced similar maximal levels of mitogenic stimulation. Skeletal muscles from mdx mice, however, released higher amounts of CME protein per gram of muscle weight compared to controls, possibly as a result of histological or physiological alterations in mdx muscle tissue. Adequate mitogenic activity in CME from mdx muscles may be related to successful muscle regeneration in mdx mice.
mdx mouse
ITGA7
Cite
Citations (4)
Thymosin beta-4 (Tbeta4) is a ubiquitous protein with many properties relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory mediators. We studied the effects of chronic administration of Tbeta4 on the skeletal and cardiac muscle of dystrophin deficient mdx mice, the mouse model of Duchenne muscular dystrophy. Female wild type (C57BL10/ScSnJ) and mdx mice, 8-10 weeks old, were treated with 150 microg of Tbeta4 twice a week for 6 months. To promote muscle pathology, mice were exercised for 30 minutes twice a week. Skeletal and cardiac muscle function were assessed via grip strength and high frequency echocardiography. Localization of Tbeta4 and amount of fibrosis were quantified using immunohistochemistry and Gomori's tri-chrome staining, respectively. Mdx mice treated with Tbeta4 showed a significant increase in skeletal muscle regenerating fibers compared to untreated mdx mice. Tbeta4 stained exclusively in the regenerating fibers of mdx mice. Although untreated mdx mice had significantly decreased skeletal muscle strength compared to untreated wild type, there were no significant improvements in mdx mice after treatment. Systolic cardiac function, measured as percent shortening fraction, was decreased in untreated mdx mice compared to untreated wild type and there was no significant difference after treatment in mdx mice. Skeletal and cardiac muscle fibrosis were also significantly increased in untreated mdx mice compared to wild type, but there was no significant improvement in treated mdx mice. In exercised dystrophin deficient mice, chronic administration of Tbeta4 increased the number of regenerating fibers in skeletal muscle and could have a potential role in treatment of skeletal muscle disease in Duchenne muscular dystrophy.
mdx mouse
Cardiac Fibrosis
Cite
Citations (19)
mdx mouse
ITGA7
Utrophin
Cite
Citations (33)
Duchenne muscular dystrophy (DMD) is a lethal X-linked genetic disorder which results in chronic degeneration of skeletal muscle, significantly impacting on the duration and quality of life. Despite the genetic defect and the missing protein dystrophin having been identified and characterised over 20 years ago, curative genetic therapies are still not clinically applicable, and corticosteroids, which are the only significantly beneficial treatment option currently available to DMD patients, are associated with several side-effects. Thus, there is a need for additional therapeutic interventions that can improve skeletal muscle function and delay the onset of severe pathology in dystrophy. The amino acid taurine is essential for normal skeletal muscle function, and has been shown to act on several factors thought to be key contributors to the development of skeletal muscle pathology in dystrophy. Moreover, as dystrophic skeletal muscle demonstrates a significant decrease in taurine content, it is possible that raising intramuscular taurine stores may preserve muscle function in dystrophy, and thus have potential therapeutic applications. Despite this, only two studies have ever examined the effect of taurine supplementation on dystrophic muscle function. The purpose of this thesis was to examine the effect of taurine on dystrophic skeletal muscle function, which was performed in three studies using the dystrophic mdx mouse as a model for DMD.
mdx mouse
Muscle disorder
Dystrophy
ITGA7
Cite
Citations (2)
Current study demonstrated the impact of heat therapy on skeletal muscle function in a model of Duchenne muscular dystrophy (DMD). The aim of this study was to: (1) examine the impact of treatment temperature on the skeletal muscle adaptation in DBA/2J mice; and (2) determine the impact of repeated HT for 3 consecutive weeks on body composition and skeletal muscle function in D2.mdx, a model of DMD. From study 1, we revealed that HT at 39℃ for 3 weeks significantly promoted relative muscle mass of both EDL and soleus muscle in DBA/2J mice. However, from study 2, HT at 39℃ for 3 weeks does not improve muscle function or increase muscle mass in a mouse model of DMD.
mdx mouse
ITGA7
Cite
Citations (0)
mdx mouse
Utrophin
ITGA7
Cite
Citations (95)
mdx mouse
ITGA7
Cite
Citations (40)
Magnetic resonance imaging allows serial visualization of living muscle. Clinically magnetic resonance imaging would be the first step in selecting a region of interest for assessment of muscle disease state and treatment effects by magnetic resonance spectroscopy. In this study, magnetic resonance imaging was used to follow dystrophy and regeneration in the mdx mouse, a genetic homologue to human Duchenne muscular dystrophy. It was hypothesized that images would distinguish normal control from mdx muscle and that regenerating areas (spontaneous and after an imposed injury) would be evident and evolve over time. T2-weighted images of hind-limb muscles were obtained on anaesthetized mice in a horizontal bore 7.1-T experimental magnet. Magnetic resonance images of mdx muscle appeared heterogeneous in comparison to homogeneous images of control muscle. Foci of high intensity in mdx images corresponded to dystrophic lesions observed in the histologic sections of the same muscles. In addition, it was possible to follow chronologically the extent of injury and repair after an imposed crush injury to mdx muscle. These results should make it possible to obtain meaningful magnetic resonance spectra from particular regions of interest in muscle as viewed in magnetic resonance images (i.e., regenerating, degenerating, normal muscle) acquired during neuromuscular diseases and treatment regimens.Key words: MRI, MRS, spectroscopy, muscular dystrophy, muscle regeneration, mdx mouse.
mdx mouse
Muscle tissue
Dystrophy
Cite
Citations (58)
mdx mouse
ITGA7
Facioscapulohumeral muscular dystrophy
Cardiac muscle
Cite
Citations (24)