9 results on '"Gilgenkrantz, H."'
Search Results
2. Long-term correction of mouse dystrophic degeneration by adenovirus-mediated transfer of a minidystrophin gene.
- Author
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Vincent N, Ragot T, Gilgenkrantz H, Couton D, Chafey P, Grégoire A, Briand P, Kaplan JC, Kahn A, and Perricaudet M
- Subjects
- Animals, Genes, Viral, Humans, Mice, Mice, Transgenic, Muscular Dystrophies genetics, Muscular Dystrophies pathology, Time Factors, beta-Galactosidase genetics, Adenoviridae genetics, Dystrophin genetics, Genetic Therapy, Muscular Dystrophies therapy, Transfection
- Abstract
Duchene muscular dystrophy (DMD) is a fatal progressive X-linked muscle disorder, caused by mutations in the dystrophin gene. We have investigated adenovirus-mediated transfer of a dystrophin minigene in a mutant mouse lacking dystrophin, the mdx mouse. We report here that six months after a single intramuscular injection of a recombinant adenovirus containing a human dystrophin minigene, a large number of dystrophin-positive fibres are still detected in the injected muscles. Moreover, although the minigene encodes a truncated protein, its expression is able to protect the fibres efficiently against the degeneration process that affects the dystrophin-deficient mdx myofibres.
- Published
- 1993
- Full Text
- View/download PDF
3. Expression of the transcripts initiated in the 62nd intron of the dystrophin gene.
- Author
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Lambert M, Chafey P, Hugnot JP, Koulakoff A, Berwald-Netter Y, Billard C, Morris GE, Kahn A, Kaplan JC, and Gilgenkrantz H
- Subjects
- Animals, Base Sequence, Child, DNA Primers, Gene Deletion, Humans, Liver metabolism, Lymphocytes metabolism, Molecular Sequence Data, Polymerase Chain Reaction, Promoter Regions, Genetic, Rats, Transcription, Genetic, Dystrophin biosynthesis, Dystrophin genetics, Gene Expression, Introns, Muscular Dystrophies genetics
- Abstract
The pattern of expression of two distal transcripts initiated in the 62nd intron of the dystrophin gene was investigated under different circumstances; (i) during the development of different rat tissues these transcripts and Dp71, a protein encoded by one of them, increased with brain development and decreased with muscle development; (ii) in cultured glial and neuronal cells, the distal promoter was coactivated with tissue-specific upstream promoters, the muscle-type promoter in glial cells and the brain-type promoter in neuronal cells, which suggests that activity of the upstream promoter does not interfere with activity of the distal promoter; (iii) in lymphoblasts of DMD patients with various deletions of the dystrophin gene, the most distal of which included the 56th intron, the production of the distal transcript was not perturbed.
- Published
- 1993
- Full Text
- View/download PDF
4. Efficient adenovirus-mediated transfer of a human minidystrophin gene to skeletal muscle of mdx mice.
- Author
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Ragot T, Vincent N, Chafey P, Vigne E, Gilgenkrantz H, Couton D, Cartaud J, Briand P, Kaplan JC, and Perricaudet M
- Subjects
- Animals, Base Sequence, Blotting, Western, Cell Line, DNA genetics, Dystrophin analysis, Fluorescent Antibody Technique, Gene Expression, Genetic Vectors, Humans, Mice, Mice, Mutant Strains, Molecular Sequence Data, Muscular Dystrophy, Animal genetics, Polymerase Chain Reaction, Sarcolemma metabolism, Adenoviridae genetics, Dystrophin genetics, Muscles metabolism, Muscular Dystrophies genetics, Transfection
- Abstract
Duchenne progressive muscular dystrophy is a lethal and common X-linked genetic disease caused by the absence of dystrophin, a 427K protein encoded by a 14 kilobase transcript. Two approaches have been proposed to correct the dystrophin deficiency in muscle. The first, myoblast transfer therapy, uses cells from normal donors, whereas the second involves direct intramuscular injection of recombinant plasmids expressing dystrophin. Adenovirus is an efficient vector for in vivo expression of various foreign genes. It has recently been demonstrated that a recombinant adenovirus expressing the lac-Z reporter gene can infect stably many mouse tissues, particularly muscle and heart. We have tested the ability of a recombinant adenovirus, containing a 6.3 kilobase pair Becker-like dystrophin complementary DNA driven by the Rous sarcoma virus promoter to direct the expression of a 'minidystrophin' in infected 293 cells and C2 myoblasts, and in the mdx mouse, after intramuscular injection. We report here that in vivo, we have obtained a sarcolemmal immunostaining in up to 50% of fibres of the injected muscle.
- Published
- 1993
- Full Text
- View/download PDF
5. [Molecular pathology of Duchenne and Becker muscular dystrophy].
- Author
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Gilgenkrantz H, Chelly J, Récan D, Chafey P, and Kaplan JC
- Subjects
- Dystrophin genetics, Humans, Muscular Dystrophies metabolism, Mutation genetics, Muscular Dystrophies genetics
- Abstract
Duchenne and Becker muscular dystrophies (DMD and BMD) are two allelic recessive X-linked disorders. Molecular deletions of various regions of the dystrophin gene are the main mutations detected in DMD and BMD patients. Molecular study of DMD and BMD DNA are instrumental to understand the pathological molecular mechanisms and the function of the protein. We describe here dystrophin and its interaction with a glycoprotein complex and we then focus on two particular patients with partial deletions of the dystrophin gene: 1) a typical Becker patient, who shows an intragenic deletion disrupting the reading frame. We describe in this case alternative splicings restoring the reading frame, which might explain the mild clinical phenotype of this patient, 2) a deletion of the distal part of the DMD gene coding for the carboxyterminal domain of the dystrophin in a young patient. The normal localization of dystrophin at the inner face of the plasma membrane in the muscle of this patient suggests that the last domain of this protein is not sufficient to anchor dystrophin at the membrane.
- Published
- 1992
6. Illegitimate transcription. Application to the analysis of truncated transcripts of the dystrophin gene in nonmuscle cultured cells from Duchenne and Becker patients.
- Author
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Chelly J, Gilgenkrantz H, Hugnot JP, Hamard G, Lambert M, Récan D, Akli S, Cometto M, Kahn A, and Kaplan JC
- Subjects
- Base Sequence, Cells, Cultured, Humans, Molecular Sequence Data, Mutation, Phenotype, Polymerase Chain Reaction, RNA Splicing, RNA, Messenger analysis, Dystrophin genetics, Muscular Dystrophies genetics, Transcription, Genetic
- Abstract
We have previously demonstrated that there is a low level of transcription of tissue-specific genes in every cell type. In this study, we have taken advantage of this phenomenon, called illegitimate transcription, to analyze the muscle-type dystrophin mRNA in easily accessible cells such as lymphoid cells, fibroblasts, and peripheral blood cells from Duchenne and Becker muscular dystrophies with known internal gene deletion. The results showed that, in the studied regions surrounding the deletions, processing of truncated transcripts is identical in specific (muscle tissue) and in nonspecific cells (lymphoid cells). In Becker cases with out-of-frame deletions, the already described alternatively spliced species found in muscle samples were also found in nonspecific cells. These results demonstrate that illegitimate transcripts are a bona fide version of tissue-specific mRNA, and that they represent a useful material to investigate the qualitative consequences of gene defects at the mRNA level.
- Published
- 1991
- Full Text
- View/download PDF
7. Effect of dystrophin gene deletions on mRNA levels and processing in Duchenne and Becker muscular dystrophies.
- Author
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Chelly J, Gilgenkrantz H, Lambert M, Hamard G, Chafey P, Récan D, Katz P, de la Chapelle A, Koenig M, and Ginjaar IB
- Subjects
- Base Sequence, Exons, Humans, Molecular Sequence Data, Muscular Dystrophies classification, Oligonucleotide Probes, RNA Splicing, Reading Frames, Restriction Mapping, Chromosome Deletion, Dystrophin genetics, Gene Amplification, Genes, Muscular Dystrophies genetics, RNA, Messenger genetics, Transcription, Genetic
- Abstract
Muscle dystrophin mRNAs from Duchenne (DMD) and Becker (BMD) patients with internal deletion of the DMD gene were quantitated and sequenced. In all cases (eight DMD and three BMD), truncated mature transcripts were found, and their amount was correlated to the clinical phenotype and to the reading frame. We focused on four cases that were apparently not in agreement with the reading frame rule. In two DMD cases, slightly reduced amounts of in-frame truncated mRNA are present but no dystrophin is detected, suggesting impaired translation and/or instability of the protein. In two BMD patients with out-of-frame deletions, the presence of minor in-frame alternatively spliced mRNA species is congruent with the observed truncated dystrophin and the mild phenotype.
- Published
- 1990
- Full Text
- View/download PDF
8. Analysis of molecular deletions with cDNA probes in patients with Duchenne and Becker muscular dystrophies.
- Author
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Gilgenkrantz H, Chelly J, Lambert M, Récan D, Barbot JC, van Ommen GJ, and Kaplan JC
- Subjects
- Adolescent, Adult, Blotting, Southern, Child, DNA Mutational Analysis, DNA Probes, Electrophoresis, Exons, Humans, Introns, Chromosome Deletion, Muscular Dystrophies genetics
- Abstract
In the course of a systematic survey of DMD and BMD patients with intronic probes and with cDNA probes covering three-fourths of the coding sequence, 45 molecular deletions within the DMD gene were investigated. Forty-two percent of the breakpoints were located in the intronic sequence containing probe P20, whereas the other deletions were widespread around the more proximal part of the gene. Most of the BMD deletions were in the P20 region. Pulsed field gel electrophoresis was used to determine the size of some deletions and allowed us to estimate the physical distance between the intronic probes JBir and P20. The reading frame was checked in 11 cases with proximal deletions and found to be disrupted in 6 of 7 DMD patients, in 1 intermediate case, and, unexpectedly, in 3 BMD patients.
- Published
- 1989
- Full Text
- View/download PDF
9. The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion.
- Author
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Koenig M, Beggs AH, Moyer M, Scherpf S, Heindrich K, Bettecken T, Meng G, Müller CR, Lindlöf M, Kaariainen H, de la Chapellet A, Kiuru A, Savontaus ML, Gilgenkrantz H, Récan D, Chelly J, Kaplan JC, Covone AE, Archidiacono N, Romeo G, Liechti-Gailati S, Schneider V, Braga S, Moser H, Darras BT, Murphy P, Francke U, Chen JD, Morgan G, Denton M, Greenberg CR, Wrogemann K, Blonden LA, van Paassen MB, van Ommen GJ, and Kunkel LM
- Subjects
- Adolescent, Child, Cloning, Molecular, DNA Probes, Deoxyribonuclease HindIII, Exons, Humans, Muscular Dystrophies classification, Muscular Dystrophies physiopathology, Reading Frames, Restriction Mapping, Transcription, Genetic, Chromosome Deletion, Dystrophin genetics, Muscular Dystrophies genetics, Mutation
- Abstract
About 60% of both Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) is due to deletions of the dystrophin gene. For cases with a deletion mutation, the "reading frame" hypothesis predicts that BMD patients produce a semifunctional, internally deleted dystrophin protein, whereas DMD patients produce a severely truncated protein that would be unstable. To test the validity of this theory, we analyzed 258 independent deletions at the DMD/BMD locus. The correlation between phenotype and type of deletion mutation is in agreement with the "reading frame" theory in 92% of cases and is of diagnostic and prognostic significance. The distribution and frequency of deletions spanning the entire locus suggests that many "in-frame" deletions of the dystrophin gene are not detected because the individuals bearing them are either asymptomatic or exhibit non-DMD/non-BMD clinical features.
- Published
- 1989
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