Mice transgenic for the human myotonic dystrophy region with expanded CTG repeats display muscular and brain abnormalities
| Autor: | Claudine Junien, Nacira Tabti, Chantal Duros, Cédric Savouret, Nicolas Sergeant, Antoine Ghestem, Hervé Seznec, Gillian Butler-Browne, Onnik Agbulut, Geneviève Gourdon, Edith Brisson, Jean-Claude Willer, Lucie Ourth, André Delacourte, Coralie Fouquet |
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| Přispěvatelé: | Bard, Genevieve, Physiologie et physiopathologie de la motricité chez l'homme, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2001 |
| Předmět: |
Male
Gene Expression CELF1 Protein Myotonia Mice chemistry.chemical_compound 0302 clinical medicine Trinucleotide Repeats Myotonic Dystrophy MBNL1 Cells Cultured In Situ Hybridization Fluorescence ComputingMilieux_MISCELLANEOUS Genetics (clinical) Mice Knockout Genetics 0303 health sciences Myotonin-protein kinase Brain General Medicine Phenotype medicine.anatomical_structure Electrophoresis Polyacrylamide Gel Female medicine.symptom Haploinsufficiency musculoskeletal diseases congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Mice Transgenic tau Proteins Protein Serine-Threonine Kinases Biology Myotonic dystrophy Myotonin-Protein Kinase 03 medical and health sciences Internal medicine medicine Animals Humans RNA Messenger Muscle Skeletal Myopathy Molecular Biology 030304 developmental biology Cell Nucleus [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health Electromyography [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health Skeletal muscle medicine.disease Endocrinology chemistry Trinucleotide Repeat Expansion 030217 neurology & neurosurgery |
| Zdroj: | Scopus-Elsevier Human Molecular Genetics Human Molecular Genetics, Oxford University Press (OUP), 2001, 10, pp.2717-2726 Human Molecular Genetics, 2001, 10, pp.2717-2726 |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/10.23.2717 |
| Popis: | The autosomal dominant mutation causing myotonic dystrophy (DM1) is a CTG repeat expansion in the 3'-UTR of the DM protein kinase (DMPK) gene. This multisystemic disorder includes myotonia, progressive weakness and wasting of skeletal muscle and extramuscular symptoms such as cataracts, testicular atrophy, endocrine and cognitive dysfunction. The mechanisms underlying its pathogenesis are complex. Recent reports have revealed that DMPK gene haploinsufficiency may account for cardiac conduction defects whereas cataracts may be due to haploinsufficiency of the neighboring gene, the DM-associated homeobox protein (DMAHP or SIX5) gene. Furthermore, mice expressing the CUG expansion in an unrelated mRNA develop myotonia and myopathy, consistent with an RNA gain of function. We demonstrated that transgenic mice carrying the CTG expansion in its human DM1 context (>45 kb) and producing abnormal DMPK mRNA with at least 300 CUG repeats, displayed clinical, histological, molecular and electrophysiological abnormalities in skeletal muscle consistent with those observed in DM1 patients. Like DM1 patients, these transgenic mice show abnormal tau expression in the brain. These results provide further evidence for the RNA trans-dominant effect of the CUG expansion, not only in muscle, but also in brain. |
| Databáze: | OpenAIRE |
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