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Results for “Muscular Dystrophy, Animal”

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At least 19 recordsLinked to original sources
PubMed2003

Duchenne's muscular dystrophy: animal models used to investigate pathogenesis and develop therapeutic strategies.

Duchenne's muscular dystrophy (DMD) is a lethal childhood disease caused by mutations of the dystrophin gene, the protein product of which, dystrophin, has a vital role in maintaining muscle structure and function. Homologues of DMD have been identified in several animals including dogs, cats, mice, fish and invertebrates. The most notable of these are the extensively studied mdx mouse, a genetic and biochemical model of the human disease, and the muscular dystrophic Golden Retriever dog, which is the nearest pathological counterpart of DMD. These models have been used to explore potential therapeutic approaches along a number of avenues including gene replacement and cell transplantation strategies. High-throughput screening of pharmacological and genetic therapies could potentially be carried out in recently available smaller models such as zebrafish and Caenorhabditis elegans. It is possible that a successful treatment will eventually be identified through the integration of studies in multiple species differentially suited to addressing particular questions.

Animals↗
PubMed1977

[Human myopathy and animal muscular dystrophy].

Two hereditary muscular dystrophies similar to human progressive muscular dystrophy (P.M.D. Duchenne type) have been isolated in animals, one in mouse, the other in chicken. The decrease in the activity of glycogenolytic enzymes is similar to that observed in denervated muscle. Isozymic fetal types for several muscular enzymes have been observed as well in chicken as in man, but this fetal type may also be found in neurogenic atrophy. The release in circulation of muscle enzymes seems more specific. But the origin of the genetic lesion is still unknown. We describe here the three different theories about this problem: i.e. neurogenic, vascular, or myogenic. This last theory implies a trouble of membrane permeability.

Adenosine Triphosphate↗
PubMed1988

Canine X-linked muscular dystrophy. An animal model of Duchenne muscular dystrophy: clinical studies.

The progression of clinical disease and serum creatine kinase (CK) levels in canine X-linked muscular dystrophy (CXMD) was studied in 7 dogs from birth to 12-14 months and in 18 dogs at varying intervals from birth to 8 weeks. One affected male was studied from age 3.5 to 6 years, and all pups were descendants of this dog. A lethal neonatal form was recognized in some pups. In the more typical form, clinical signs of stunting, weakness and gait abnormalities were evident by 6-9 weeks and were progressive, leading to marked muscle atrophy, fibrosis and contractures by 6 months. Serum CK levels were markedly elevated, such that affected pups could be identified by 1 week. CK values increased until 6-8 weeks, then plateaued at approx. 100 times normal. Affected females and beagle-cross dogs were less severely affected than large breed-cross dogs. In the 2 adult dogs with cardiac insufficiency CK levels had decreased to 5-15 times normal. These studies show that CXMD and Duchenne muscular dystrophy have striking phenotypic as well as genotypic similarities. In addition, these studies of CXMD suggest that in females and in smaller dogs the same genetic defect results in a less severe clinical disease.

Age Factors↗
PubMed1992

An error in dystrophin mRNA processing in golden retriever muscular dystrophy, an animal homologue of Duchenne muscular dystrophy.

Golden retriever muscular dystrophy (GRMD) is a spontaneous, X-linked, progressively fatal disease of dogs and is also a homologue of Duchenne muscular dystrophy (DMD). Two-thirds of DMD patients carry detectable deletions in their dystrophin gene. The defect underlying the remaining one-third of DMD patients is undetermined. Analysis of the canine dystrophin gene in normal and GRMD dogs has failed to demonstrate any detectable loss of exons. Here, we have demonstrated a RNA processing error in GRMD that results from a single base change in the 3' consensus splice site of intron 6. The seventh exon is then skipped, which predicts a termination of the dystrophin reading frame within its N-terminal domain in exon 8. This is the first example of dystrophin deficiency caused by a splice-site mutation.

Amino Acid Sequence↗
PubMed2005

What do animal models have to tell us regarding Duchenne muscular dystrophy?

Animal models of DMD have played, and will continue to play, a key role in the understanding of the pathogenesis and treatment of Duchenne muscular dystrophy (DMD). The mdx mouse and GRMD dog are spontaneous dystrophin deficient mutants and have been the most widely used models to date. A number of other murine models have been created by exposure to mutagens or genetic manipulation. The animal models have allowed the development of a number of promising experimental therapeutic approaches to DMD that are now entering clinical trial, the majority of which would not have been developed without their use. However, there has been much debate about the merits of the different animal models, which will only be finally clear as we learn from the initial human clinical trials.

Animals↗
PubMed1992

Canine X-linked muscular dystrophy as an animal model of Duchenne muscular dystrophy: a review.

Canine X-linked muscular dystrophy is a spontaneously occurring, progressive, degenerative myopathy of dogs that is clinically and pathologically similar to Duchenne muscular dystrophy in man. The molecular basis for the disease has been shown to be a lack of dystrophin, the protein product of the Duchenne muscular dystrophy gene. Breeding colonies of dystrophic dogs have been established. This report reviews the findings of genetic, clinical, pathologic, molecular biologic, and immunocytochemical studies of the canine model, and compares the features of the canine disease to those of Duchenne dystrophy in man.

Animals↗
PubMed2004

The dystrophin glycoprotein complex: signaling strength and integrity for the sarcolemma.

The dystrophin glycoprotein complex (DGC) is a specialization of cardiac and skeletal muscle membrane. This large multicomponent complex has both mechanical stabilizing and signaling roles in mediating interactions between the cytoskeleton, membrane, and extracellular matrix. Dystrophin, the protein product of the Duchenne and X-linked dilated cardiomyopathy locus, links cytoskeletal and membrane elements. Mutations in additional DGC genes, the sarcoglycans, also lead to cardiomyopathy and muscular dystrophy. Animal models of DGC mutants have shown that destabilization of the DGC leads to membrane fragility and loss of membrane integrity, resulting in degeneration of skeletal muscle and cardiomyocytes. Vascular reactivity is altered in response to primary degeneration in striated myocytes and arises from a vascular smooth muscle cell-extrinsic mechanism.

Animals↗
PubMed2002

Pre-clinical trials in Duchenne dystrophy: what animal models can tell us about potential drug effectiveness.

The symptomatic pharmacological therapy of Duchenne dystrophy is poor, glucocorticoids being the sole compounds showing a certain efficacy, although their use is restricted by serious side effects. Pre-clinical trials of prompt-to-use drugs need reliable animal models of the human disease to predict drug effectiveness in patients. The exercised mdx mouse develops a typical pattern of muscle weakness in vivo, which has already been used as an index on which to evaluate drug effectiveness. We have demonstrated that the macroscopic conductance to chloride ion, an index of degeneration-regeneration events occurring in mdx mouse muscles, is specifically impaired by a chronic exercise protocol and is sensitive to the action of in vivo administered drugs acting either by stimulating regeneration (insulin-like growth factor-1 and steroids) or by counteracting calcium-induced degeneration or inflammation (Taurine and steroids). The monitoring of conductance to chloride ion also allows the evaluation of false positive compounds, effective on mouse strength in vivo but not at muscle level, and the functional correlation with other cellular parameters.

Adrenal Cortex Hormones↗
PubMed1989

Animal models of Duchenne and Becker muscular dystrophy.

Two animal models have been shown to be related to Duchenne and Becker muscular dystrophy at the molecular level. The mdx mouse is characterized by early onset of muscle degeneration and very mild clinical disease. The disease is minimally progressive and fibrosis of muscle is absent. Linkage studies, absence of dystrophin, and reduced levels of message indicate that the mutation in mdx lies in the gene for dystrophin, the gene that is defective in Duchenne and Becker muscular dystrophy. The xmd dog develops lesions that are essentially indistinguishable from those of Duchenne dystrophy, and there is progressive fibrosis and destruction of muscle tissue. Affected dogs develop severe clinical disease. The absence of dystrophin and its message in muscle, and the linkage of RFLPs recognized by Duchenne cDNA probes, indicate that the mutation in the xmd dog lies in the gene for dystrophin. Exploitation of these models should lead to a greater understanding of molecular and cellular events involved in the pathogenesis of Duchenne and Becker muscular dystrophies.

Animals↗
PubMed1976

Muscular dystrophy of mink: a new animal model.

Muscular dystrophies comprise an important group of inherited disorders of man. Although the disease has been studied extensively, little is known about the underlying primary pathomechanisms. Consequently, treatment of patients is difficult and prognosis is poor. An animal model of muscular dystrophy is a useful research tool for approaching the basic problems of pathogenesis in muscle diseases. An inherited progressive muscular dystrophy of mink which resembles the amyotonic forms of human muscular dystrophy is currently under study. Clinically, the earliest sign is progressive muscular weakness and atrophy. Muscle enzyme activities in serum are usually elevated to pathologic levels. Urinary creatine/creatinine ratio is elevated. Pathologic changes are limited to skeletal muscle and are typical of those seen in amyotonic forms of human muscular dystrophy. These changes include variation in diameter size of muscle fibers, centralized nuclei, floccular and hyaline degeneration of scattered muscle fibers, increase in connective tissue in endomysial and perimysial areas, and regenerative attempts. Both type I and type II muscle fibers are involved in the disease process. Genetic studies indicate an autosomal recessive mode of inheritance. Although the primary defect in muscular dystrophy is traditionally thought to reside in skeletal muscle, recent studies have produced theories of primary involvement of other tissues and organ systems. These theories are presented and relationships to the traditional theory are discussed.

Animals↗
PubMed1981

Thymic mast cell deficiency in avian muscular dystrophy.

In animals with hereditary muscular dystrophy there are thymic abnormalities which may be of etiological significance in the dystrophic process. This study investigated mast cell number and histamine levels in the thymus of normal and dystrophic chickens. For comparison, other lymphoid tissues, namely the spleen and the bursa of Fabricius, and non-lymphoid tissues including the comb and pectoralis major muscle, were similarly studied. Our results show that the thymus of dystrophic adult birds has a deficiency in both mast cell number and histamine content. In the bursa of Fabricius of dystrophic birds a significant elevation in histamine content (microgram/g) was attributed to the abnormally small size of this organ, rather than to an absolute mast cell increase. The deficiency in thymic mast cell number in dystrophic chickens may be significant in the postulated abnormal thymus-muscle interaction of the dystrophic process.

Animals↗
PubMed2001

The organisation of spinal projecting brainstem neurons in an animal model of muscular dystrophy. A retrograde tracing study on mdx mutant mice.

Previous studies we performed on the mdx mouse demonstrated marked central nervous system alterations in this model of human Duchenne muscular dystrophy, such as reduction in number and pathological changes of cortico-spinal neurons. Prompted by these findings we extended the survey of the mdx brain to the major brainstem-descending pathways: the rubro-, vestibulo-, reticulo-, and raphe-spinal projections. Horseradish peroxidase microinjections were performed in the cervical spinal cord of mdx and control mice. The rubro-spinal neurons were found to be significantly reduced in mutants compared to controls. The vestibulo-spinal, reticulo-spinal, and raphe-spinal cell populations, though less numerous in mdx than in control mice, were instead substantially spared. Our data further unveil the selective nature of mdx brain damage indicating a marked and selective involvement of the highest centers for motor control.

Animals↗