Utilization of an Antibody Specific for Human Dystrophin to Follow Myoblast Transplantation in Nude Mice

Human myoblasts were transplanted in nude mice. The efficacy of these transplantations was analyzed using a monoclonal antibody (NCLDys3) specific for human dystrophin. This antibody did not reveal any dystrophin in nude mice that did not receive a human myoblast transplantation. However, about 30 days after a human myoblast transplantation, dystrophin-positive muscle fibers were observed. They were not abundant, and were present either in small clusters or isolated. This technique follows the fate of myoblast transplantation in animals that already have dystrophin, and distinguishes between new dystrophin-positive fibers due to the transplantation and the revertant fibers in mdx mice. Moreover, this technique does not require any labelling of the myoblasts before transplantation. It can also be used to detect dystrophin produced following the fusion of myoblasts transfected with the human dystrophin gene.

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Dystrophin-positive muscle fibers following C2 myoblast transplantation into mdx nude mice

Acta Neuropathologica ◽

10.1007/bf00318571 ◽

1995 ◽

Vol 90 (6) ◽

pp. 592-600 ◽

Cited By ~ 3

Author(s):

Yasuko Hagiwara ◽

Yuji Mizuno ◽

Masakazu Takemitsu ◽

Tetsuya Matsuzaki ◽

Ikuya Nonaka ◽

...

Keyword(s):

Nude Mice ◽

Muscle Fibers ◽

Myoblast Transplantation

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Dystrophin-positive muscle fibers following C2 myoblast transplantation into mdx nude mice

Acta Neuropathologica ◽

10.1007/s004010050373 ◽

1995 ◽

Vol 90 (6) ◽

pp. 592-600 ◽

Cited By ~ 1

Author(s):

Y. Hagiwara ◽

Yuji Mizuno ◽

Masakazu Takemitsu ◽

Tetsuya Matsuzaki ◽

Ikuya Nonaka ◽

...

Keyword(s):

Nude Mice ◽

Muscle Fibers ◽

Myoblast Transplantation

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

AJP Cell Physiology ◽

10.1152/ajpcell.00112.2002 ◽

2002 ◽

Vol 283 (3) ◽

pp. C773-C784 ◽

Cited By ~ 41

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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Autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models

JRSM Cardiovascular Disease ◽

10.1177/2048004019879581 ◽

2019 ◽

Vol 8 ◽

pp. 204800401987958

Author(s):

HR Spaulding ◽

C Ballmann ◽

JC Quindry ◽

MB Hudson ◽

JT Selsby

Keyword(s):

Skeletal Muscle ◽

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Disease Progression ◽

Gene Mutations ◽

Dystrophin Gene ◽

Mdx Mice ◽

Dystrophin Deficiency ◽

Muscle Wasting Disease ◽

Dystrophin Protein

Background Duchenne muscular dystrophy is a muscle wasting disease caused by dystrophin gene mutations resulting in dysfunctional dystrophin protein. Autophagy, a proteolytic process, is impaired in dystrophic skeletal muscle though little is known about the effect of dystrophin deficiency on autophagy in cardiac muscle. We hypothesized that with disease progression autophagy would become increasingly dysfunctional based upon indirect autophagic markers. Methods Markers of autophagy were measured by western blot in 7-week-old and 17-month-old control (C57) and dystrophic (mdx) hearts. Results Counter to our hypothesis, markers of autophagy were similar between groups. Given these surprising results, two independent experiments were conducted using 14-month-old mdx mice or 10-month-old mdx/Utrn± mice, a more severe model of Duchenne muscular dystrophy. Data from these animals suggest increased autophagosome degradation. Conclusion Together these data suggest that autophagy is not impaired in the dystrophic myocardium as it is in dystrophic skeletal muscle and that disease progression and related injury is independent of autophagic dysfunction.

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