Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Duchenne and the less severe Becker form of muscular dystrophy (DMD,BMD) result from genetic deficiency in the level and/or activity of the protein dystrophin. The recent availability of cDNA based minigenes encoding recombinant dystrophin polypeptides has raised the possibility of somatic gene transfer as a therapeutic approach to treat dystrophin deficiency. In this respect, the mdx mouse provides a useful model of DMD exhibiting features characteristic of both the early myopathic and later fibrotic phases of the human disease. Using a mutated human cDNA, compatible in size with virus-based somatic gene transfer vectors, the pathophysiological consequences of restoring dystrophin expression have been examined in transgenic mdx mice. Transgene expression was correlated with a marked reduction of the skeletal myofibre necrosis and regeneration which is a major feature of the dystrophin-deficient phenotype in young mdx mice. The cDNA construct which is based on a very mild BMD phenotype thus encodes a highly functional dystrophin molecule whose reduced size renders it an attractive candidate for development as a therapeutic gene transfer reagent.
Hum Mol Genet 1992 Apr
PMID:Human dystrophin expression corrects the myopathic phenotype in transgenic mdx mice. 130 Nov 34

Both normal and pathological transcripts of tissue-specific genes may be detected by polymerase chain reaction (PCR) amplification in tissues not normally considered to express the gene product. The exploitation of constitutive basal mRNA levels ("ectopic" transcription) would be a major boon to diagnostic medicine since it promises both to simplify the analysis of complex genes and to avoid the requirement for an expressing tissue that is sometimes obtainable only by biopsy. We have demonstrated the feasibility of this novel strategy by characterizing a mutation in the X-chromosomal Duchenne (or Becker) muscular dystrophy (DMD/BMD) gene encoding dystrophin. The massive size of this gene has in the past often hindered carrier detection due to the high frequency of recombination and the high proportion of new mutations. In this study a deletion was identified in both a BMD patient and a heterozygous carrier using only a minimal volume of peripheral blood. Following specifically primed reverse transcription of lymphocyte RNA, the relevant region of the pathological cDNA was PCR-amplified. Sequence analysis indicated an in-frame deletion of exons 45 to 47.
Mol Biol Med 1990 Dec
PMID:Characterization of pathological dystrophin transcripts from the lymphocytes of a muscular dystrophy carrier. 170 53

The present study was undertaken to investigate whether vascular cells show insulin-like growth factor I (IGF-I; somatomedin C) immunoreactivity under normal conditions and/or during angiogenesis in humans and animals, as the trophic peptide IGF-I is considered important for cell growth and differentiation. In adult animals normal blood vessels, i.e., arteries, veins, and capillaries, did not show any IGF-I immunoreactivity. In newborn animals every vascular cell showed IGF-I immunoreactivity; the frequency and intensity thereafter decreased and eventually vanished as the animals approached maturity. Injury of a tissue or organ rapidly induced extensive blood vessel formation and such new blood vessels transiently expressed IGF-I immunoreactivity. Endothelial cells in budding capillaries showed distinct cytoplasmic IGF-I immunoreactivity, as did endothelial cells, smooth muscle cells, and fibroblast in newly formed arteries and veins. In biopsies of human tissue, transient IGF-I immunoreactivity was evident in vascular cells during angiogenesis after injury, as it also was in granulation tissue, skin wounds, and scar capsules around implants. Increased IGF-I immunoreactivity was further demonstrated in vascular cells in biopsies from patients with other changes involving blood vessel formation, e.g., nasal polyps, and in specimens from patients with arteritis, tendonitis, synovitis, Wegener's granulomatosis, idiopathic midline destructive disease, neurofibromatosis (von Recklinghausen's disease), and muscular dystrophy. It is concluded that during angiogenesis, obviously irrespective of inducing factors and mechanisms, vascular wall cells transiently show IGF-I immunoreactivity.
Exp Mol Pathol 1989 Feb
PMID:Transient expression of insulin-like growth factor I immunoreactivity by vascular cells during angiogenesis. 246 16

The murine locus corresponding to the human Duchenne/Becker muscular dystrophy (DMD) gene has been regionally mapped on the mouse X chromosome by hybridizing DNA from interspecies mouse crosses with a cDNA clone for the mouse Dmd gene. The results demonstrate that the relative organization of genes on the murine and human X chromosomes is more divergent than has previously been postulated. Furthermore, the mouse Dmd gene maps to a similar region of the X chromosome as does the mouse muscular dystrophy mutation mdx, providing further evidence that the mdx mutant may be a murine equivalent of human DMD. However, Southern analysis of portions of the mouse Dmd gene has not yet revealed any differences between mdx and wild-type mice.
Somat Cell Mol Genet 1987 Nov
PMID:Regional localization of the murine Duchenne muscular dystrophy gene on the mouse X chromosome. 289 Feb 15

Eosinophilic enteritis and eosinophilia, in addition to muscular dystrophy and occasionally liver necrosis, were experimentally induced in male Sprague-Dawley rats with a vitamin E- and selenium-deficient diet (basal diet) for 9 weeks. Cecum and ileum were affected more frequently and severely than other segments of the gastrointestinal tract. Eosinophils were multifocally or diffusely distributed in the intestinal wall but were most severe in the muscular layer and in the submucosa. Eosinophils were also present in stomach, liver with massive hepatocellular necrosis, and skeletal muscle with marked myonecrosis. Eosinophilic enteritis and eosinophilia were not observed in rats fed the basal diet supplemented with either vitamin E (100 or 200 ppm) or selenium (0.1 or 1.0 ppm). Eosinophilic enteritis, eosinophilia, and muscular dystrophy regressed when vitamin E- and selenium-deficient rats were subsequently fed either the vitamin E- or selenium-supplemented diet for 4-5 weeks. These findings suggest that vitamin E and selenium deficiency may play a role in the development of a diffuse type of eosinophilic enteritis and eosinophilia.
Exp Mol Pathol 1988 Apr
PMID:Induction of eosinophilic enteritis and eosinophilia in rats by vitamin E and selenium deficiency. 335 Jan 41

The activity of glycerophosphorylcholine synthetase, a newly discovered enzyme involved in the synthesis of acyl-specific phosphatidylcholines, is reported in rat lung and muscle. Its subcellular location appears to be mitochondrial. The implication of these findings in the synthesis of lung surfactant and the pathology of muscular dystrophy are discussed.
Mol Cell Biochem 1986 Aug
PMID:De novo sn-glycerol-3-phosphorylcholine synthetase activity in lung and muscle and its subcellular location. 377 85

Murine dystrophia muscularis-2J (dy2J) is an autosomal recessive disorder characterized by muscular dystrophy and dysmyelination of peripheral nerve. Biochemical characterization of dy2J mice revealed the expression of a mutant laminin alpha 2 chain with a smaller molecular weight in the basal lamina of striated muscle and peripheral nerve. DNA sequencing of the alpha 2 chain cDNA amplified by RT-PCR from dy2J mice identified a novel and predominant transcript with a 171 base in-frame deletion. We also confirmed an underlying splice donor site mutation in the alpha 2 chain gene of the dy2J mouse. Translation of this variant transcript would result in the expression of a truncated alpha 2 chain having a 57 amino acid deletion (residues 34-90) and a substitution of Gln91Glu in the N-terminal domain VI, which is presumed to be involved in self-aggregation of laminin heterotrimers. Thus, the mutant alpha 2 chain could disrupt the formation of the laminin network and lead to muscle cell degeneration. Our results provide a molecular basis of muscular dystrophy and dysmyelination of peripheral nerve.
Hum Mol Genet 1995 Jun
PMID:Identification of a novel mutant transcript of laminin alpha 2 chain gene responsible for muscular dystrophy and dysmyelination in dy2J mice. 765 59

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant muscular dystrophy which presents typically after the age of 50 with progressive eyelid drooping and an increasing difficulty in swallowing. Though OPMD has a world-wide incidence, it is more common in the French Canadian population. We have identified a homogeneous group of families and studied 166 polymorphic markers as part of a genome search before establishing linkage to chromosome 14. We determined that the OPMD locus maps to a less than 5 cM region of chromosome 14q11.2-q13. The maximum two-point lod score in three French Canadian families of 14.73 (theta = 0.03) was obtained for an intronic cardiac beta myosin heavy chain gene (MYH7) marker. The regional localization for the OPMD locus raises the intriguing possibility that either the cardiac alpha or beta myosin heavy chain genes may play a role in this disease.
Hum Mol Genet 1995 Mar
PMID:The oculopharyngeal muscular dystrophy locus maps to the region of the cardiac alpha and beta myosin heavy chain genes on chromosome 14q11.2-q13. 779 98

The C-terminal domain of dystrophin is alternatively spliced to produce a variety of tissue and developmental stage-specific isoforms. Recent studies suggest that the C-terminal domain binds to the dystrophin-associated glycoprotein complex (DGC) in muscle, but little is known about the functional significance of the alternative splicing or what role individual isoforms may play in specific tissues. The major dystrophin transcript in brain lacks exons 71-74, and encodes an isoform not observed in skeletal muscle. To explore the capacity of this truncated isoform to function in muscle, we have generated transgenic mice expressing a murine dystrophin mini-gene missing exons 71-74. Uniform expression of this construct on a mutant mdx mouse background results in normal muscle morphology and physiology, and prevents the development of muscular dystrophy. These mice also display normal expression and localization of the DGC, suggesting that the alternatively spliced exons are not required for dystrophin function in skeletal muscle. An additional line of mice was analyzed that had a mosaic pattern of expression. These mice display a markedly milder phenotype than mdx mice, despite the expression of dystrophin in only half the muscle fibers. These results indicate that viral delivery of dystrophin to a simple majority of fibers in a muscle group would greatly reduce the dystrophic pathology associated with Duchenne muscular dystrophy.
Hum Mol Genet 1994 Oct
PMID:Prevention of dystrophic pathology in mdx mice by a truncated dystrophin isoform. 784 95

We have recently demonstrated the specific deficiency for the 50 kDa dystrophin-associated glycoprotein (50DAG) in Algerian patients afflicted with severe childhood autosomal recessive muscular dystrophy with DMD-like phenotype (SCARMD). A similar disease affecting Tunisian patients was linked to chromosome 13q but the status of the 50DAG was not investigated. Here we show by linkage analysis of Algerian families that the genetic defect which leads, either directly or indirectly, to the deficiency of the 50DAG in skeletal muscle is localized to the proximal part of chromosome 13q. We have not found any evidence of genetic heterogeneity among the thirteen families studied. It remains to be demonstrated whether the 50DAG gene maps at 13q12, and to determine if it is mutated in this disease.
Hum Mol Genet 1993 Sep
PMID:Severe childhood autosomal recessive muscular dystrophy with the deficiency of the 50 kDa dystrophin-associated glycoprotein maps to chromosome 13q12. 824 65


1 2 3 4 5 6 7 8 9 10 Next >>