Duchenne muscular dystrophy: Deficiency of dystrophin at the muscle cell surface

Bonilla, Eduardo; Samitt, Craig E.; Miranda, Armand F.; Hays, Arthur P.; Salviati, G.; DiMauro, Salvatore; Kunkel, Louis M.; Hoffman, Eric P.; Rowland, Lewis P.

doi:10.1016/0092-8674(88)90065-7

Cited by 572 publications

(244 citation statements)

References 23 publications

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“…Dystrophin, a 400 kDa protein with amino acid sequence identity to the spectrin family of membrane cytoskeletal proteins [3,4], is found in the sarcolemmal membrane of normal skeletal muscle [5]. It is absent from the skeletal muscle of both DMD humans and mdx mice [6][7][8][9]. Although muscular dystrophies are characterized by muscle degeneration, a major difference between the mdx mouse and the DMD human syndromes is the successful muscle fibre regeneration that occurs in the mdx mice, which restores muscle histology and function to approximate normality [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Expression of the glucose transporter GLUT4 in the muscular dystrophic mdx mouse

Olichon-Berthe

Gautier

Obberghen

et al. 1993

Biochemical Journal

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Glucose transporter protein levels have been investigated in mdx and control (C57Bl/1O) mice. Crude membrane fractions (microsomes plus plasma membranes) were prepared from skeletal muscle, heart, diaphragm and brain of 5-6-week-old and 6-7-month-old control and mdx mice. Using Western blot analysis with C-terminal-specific anti-peptide antibodies, we investigated the glucose transporters GLUT4 in the different muscle tissues and GLUTI in brain. In skeletal tissue from the hindlegs, GLUT4 was increased by -55 % in mdx mice compared with control mice at both ages studied. In the diaphragm, the amount of GLUT4 protein was unchanged in young mdx mice, and was decreased by 37.4 + 4.7% in older mice compared with agematched control mice. No difference was observed between mdx and control mice in the amounts of GLUT4 and GLUTI in heart and brain preparations respectively. To determine whether the change in GLUT4 protein observed in the diaphragm and

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Section: Introductionmentioning

confidence: 99%

Expression of the glucose transporter GLUT4 in the muscular dystrophic mdx mouse

Olichon-Berthe

Gautier

Obberghen

et al. 1993

Biochemical Journal

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“…It is the most common muscular dystrophy, affecting one in 3500 male births, 1 and is characterized by the lack of dystrophin at the muscle fiber membrane. 2,3 Dystrophin is the essential link between the subsarcolemmal cytoskeleton and the extracellular matrix. 4,5 Disruption of this link results in fiber necrosis and progressive muscle weakness, which begins in early childhood.…”

mentioning

confidence: 99%

Systemic Delivery of Allogenic Muscle Stem Cells Induces Long-Term Muscle Repair and Clinical Efficacy in Duchenne Muscular Dystrophy Dogs

Rouger

Larcher

Dubreil

et al. 2011

The American Journal of Pathology

100

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Duchenne muscular dystrophy (DMD) is a genetic progressive muscle disease resulting from the lack of dystrophin and without effective treatment. Adult stem cell populations have given new impetus to cellbased therapy of neuromuscular diseases. One of them, muscle-derived stem cells, isolated based on delayed adhesion properties, contributes to injured muscle repair. However, these data were collected in dystrophic mice that exhibit a relatively mild tissue phenotype and clinical features of DMD patients. Here, we characterized canine delayed adherent stem cells and investigated the efficacy of their systemic delivery in the clinically relevant DMD animal model to assess potential therapeutic application in humans. Delayed adherent stem cells, named MuStem cells (muscle stem cells), were isolated from healthy dog muscle using a preplating technique. In vitro, MuStem cells displayed a large expansion capacity, an ability to proliferate in suspension, and a multilineage differentiation potential. Phenotypically, they corresponded to early myogenic progenitors and uncommitted cells. When injected in immunosuppressed dystrophic dogs, they contributed to myofiber regeneration, satellite cell replenishment, and dystrophin expression. Importantly, their systemic delivery resulted in long-term dystrophin expression, muscle damage course limitation with an increased regeneration activity and an interstitial expansion restriction, and persisting stabilization of the dog's clinical status. These results demonstrate that MuStem cells could provide an attractive therapeutic avenue for DMD patients.

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“…In contrast to dystrophin which is found on the cytoplasmic face of the sarcolemma in normal muscles [12,13,14], utrophin accumulates specifically at the levels of the neuromuscular synapse and myotendinous junction in both normal and dystrophic adult muscles [15][16][17][18][19][20][21][22][23][24]. Additional studies have shown that utrophin is present in greater amounts in small caliber muscle fibers of mdx mice [18,25], small or regenerating muscle fibers of *Corresponding author.…”

Section: Introductionmentioning

confidence: 99%

Expression of utrophin and its mRNA in denervated mdx mouse muscle

et al. 1995

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Utrophin is a large cytoskeletal protein which shows high homology to dystrophin. In contrast to the sarcolemmal distribution of dystrophin, utrophin accumulates at the postsynaptic membrane of the neuromuscular junction. Because of its localization within this compartment of muscle fibers, expression of utrophin may be significantly influenced by the presence of the motor nerve. We tested this hypothesis by denervating muscles of mdx mouse and monitoring levels of utrophin and its mRNA by immunofluorescence, immunobiotting and RT-PCR. A significant increase in the number of utrophin positive fibers was observed by immunofluorescence 3 to 21 days after sectioning of the sciatic nerve. Quantitative analyses of utrophin and its transcripts in hindlimb muscles denervated for two weeks showed only a moderate increase in the levels of both utrophin (~ 2-fold) and its transcript (-60 to 90%). The present data suggest that although utrophin is a component of the postsynaptic membrane, its neural regulation is distinct from that of the acetylcholine receptor.

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Duchenne muscular dystrophy: Deficiency of dystrophin at the muscle cell surface

Cited by 572 publications

References 23 publications

Expression of the glucose transporter GLUT4 in the muscular dystrophic mdx mouse

Expression of the glucose transporter GLUT4 in the muscular dystrophic mdx mouse

Systemic Delivery of Allogenic Muscle Stem Cells Induces Long-Term Muscle Repair and Clinical Efficacy in Duchenne Muscular Dystrophy Dogs

Expression of utrophin and its mRNA in denervated mdx mouse muscle

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