DM1 CTG expansions affect insulin receptor isoforms expression in various tissues of transgenic mice
| Autor: | Mário Gomes-Pereira, Geneviève Gourdon, Céline Guiraud-Dogan, Edith Brisson, Aline Huguet, Guillaume Bassez, Claudine Junien |
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| Přispěvatelé: | Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'histologie-Hôpital Henri Mondor |
| Rok vydání: | 2007 |
| Předmět: |
Untranslated region
Aging Adipose tissue Splicing Mice 0302 clinical medicine Insulin Secretion Transgenic mice Insulin Myotonic Dystrophy Protein Isoforms Transgenes ComputingMilieux_MISCELLANEOUS 0303 health sciences biology Life Sciences Organ Specificity RNA splicing Molecular Medicine Genetically modified mouse musculoskeletal diseases congenital hereditary and neonatal diseases and abnormalities Hypothalamus Mice Transgenic Protein Serine-Threonine Kinases Myotonic dystrophy Myotonin-Protein Kinase 03 medical and health sciences Trinucleotide repeat medicine Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology RNA Messenger Molecular Biology Pancreas 030304 developmental biology Gene Expression Profiling Alternative splicing Glucose Tolerance Test medicine.disease Molecular biology Receptor Insulin Insulin receptor Alternative Splicing Glucose biology.protein Mutant Proteins Trinucleotide repeat expansion Trinucleotide Repeat Expansion 030217 neurology & neurosurgery |
| Zdroj: | Biochimica et Biophysica Acta-Molecular Basis of Disease Biochimica et Biophysica Acta-Molecular Basis of Disease, Elsevier, 2007, 1772 (11-12), pp.1183. ⟨10.1016/j.bbadis.2007.08.004⟩ |
| ISSN: | 0006-3002 0925-4439 |
| DOI: | 10.1016/j.bbadis.2007.08.004⟩ |
| Popis: | Myotonic dystrophy (DM1) is a dominant autosomal multisystemic disorder caused by the expansion of an unstable CTG trinucleotide repeat in the 3′ untranslated region of the DMPK gene. Nuclear accumulation of the enlarged CUG-containing DMPK transcripts has a deleterious effect on the regulation of alternative splicing of some RNAs and has a central role in causing the symptoms of DM1. In particular, Insulin Receptor (IR) mRNA splicing defects have been observed in the muscle of DM1 patients. In this study, we have investigated IR splicing in insulin-responsive tissues (i.e. skeletal muscles, adipose tissue, liver) and pancreas and we have studied glucose metabolism in mice carrying the human genomic DM1 region with expanded (> 350 CTG) or normal (20 CTG) repeats and in wild-type mice. Mice carrying DM1 expansions displayed a tissue- and age-dependent abnormal regulation of IR mRNA splicing in all the tissues that we investigated. Furthermore, these mice showed a basal hyperglycemia and glucose intolerance which disappeared with age. Our findings show that deregulation of IR splicing due to the DM1 mutation can occur in different mouse tissues, suggesting that CTG repeat expansions might also result in IR misplicing not only in muscles but also in other tissues in DM1 patients. |
| Databáze: | OpenAIRE |
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