Transgenic expression of an expanded (GCG)13 repeat PABPN1 leads to weakness and coordination defects in mice
Oculopharyngeal muscular dystrophy (OPMD) is a late-onset disorder caused by a (GCG)n trinucleotide repeat expansion in the poly(A) binding protein nuclear-1 (PABPN1) gene, which in turn leads to an expanded polyalanine tract in the protein. We generated transgenic mice expressing either the wild ty...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2005-04-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999610400227X |
| _version_ | 1831583047979368448 |
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| author | Patrick Dion Vijayalakshmi Shanmugam Claudia Gaspar Christiane Messaed Inge Meijer André Toulouse Janet Laganiere Julie Roussel Daniel Rochefort Simon Laganiere Carol Allen George Karpati Jean-Pierre Bouchard Bernard Brais Guy A. Rouleau |
| author_facet | Patrick Dion Vijayalakshmi Shanmugam Claudia Gaspar Christiane Messaed Inge Meijer André Toulouse Janet Laganiere Julie Roussel Daniel Rochefort Simon Laganiere Carol Allen George Karpati Jean-Pierre Bouchard Bernard Brais Guy A. Rouleau |
| author_sort | Patrick Dion |
| collection | DOAJ |
| description | Oculopharyngeal muscular dystrophy (OPMD) is a late-onset disorder caused by a (GCG)n trinucleotide repeat expansion in the poly(A) binding protein nuclear-1 (PABPN1) gene, which in turn leads to an expanded polyalanine tract in the protein. We generated transgenic mice expressing either the wild type or the expanded form of human PABPN1, and transgenic animals with the expanded form showed clear signs of abnormal limb clasping, muscle weakness, coordination deficits, and peripheral nerves alterations. Analysis of mitotic and postmitotic tissues in those transgenic animals revealed ubiquitinated PABPN1-positive intranuclear inclusions (INIs) in neuronal cells. This latter observation led us to test and confirm the presence of similar INIs in postmortem brain sections from an OPMD patient. Our results indicate that expanded PABPN1, presumably via the toxic effects of its polyalanine tract, can lead to inclusion formation and neurodegeneration in both the mouse and the human. |
| first_indexed | 2024-12-17T20:35:21Z |
| format | Article |
| id | doaj.art-f2ced499cef7486292cc5050dee39082 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T20:35:21Z |
| publishDate | 2005-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-f2ced499cef7486292cc5050dee390822022-12-21T21:33:28ZengElsevierNeurobiology of Disease1095-953X2005-04-01183528536Transgenic expression of an expanded (GCG)13 repeat PABPN1 leads to weakness and coordination defects in micePatrick Dion0Vijayalakshmi Shanmugam1Claudia Gaspar2Christiane Messaed3Inge Meijer4André Toulouse5Janet Laganiere6Julie Roussel7Daniel Rochefort8Simon Laganiere9Carol Allen10George Karpati11Jean-Pierre Bouchard12Bernard Brais13Guy A. Rouleau14McGill University Health Center Research Institute and the Centre for Research in Neurosciences, McGill University, 1650 Cedar Avenue (L7-224), Montréal, Québec, Canada, H3G 1A4McGill University Health Center Research Institute and the Centre for Research in Neurosciences, McGill University, 1650 Cedar Avenue (L7-224), Montréal, Québec, Canada, H3G 1A4McGill University Health Center Research Institute and the Centre for Research in Neurosciences, McGill University, 1650 Cedar Avenue (L7-224), Montréal, Québec, Canada, H3G 1A4McGill University Health Center Research Institute and the Centre for Research in Neurosciences, McGill University, 1650 Cedar Avenue (L7-224), Montréal, Québec, Canada, H3G 1A4McGill University Health Center Research Institute and the Centre for Research in Neurosciences, McGill University, 1650 Cedar Avenue (L7-224), Montréal, Québec, Canada, H3G 1A4McGill University Health Center Research Institute and the Centre for Research in Neurosciences, McGill University, 1650 Cedar Avenue (L7-224), Montréal, Québec, Canada, H3G 1A4McGill University Health Center Research Institute and the Centre for Research in Neurosciences, McGill University, 1650 Cedar Avenue (L7-224), Montréal, Québec, Canada, H3G 1A4McGill University Health Center Research Institute and the Centre for Research in Neurosciences, McGill University, 1650 Cedar Avenue (L7-224), Montréal, Québec, Canada, H3G 1A4McGill University Health Center Research Institute and the Centre for Research in Neurosciences, McGill University, 1650 Cedar Avenue (L7-224), Montréal, Québec, Canada, H3G 1A4McGill University Health Center Research Institute and the Centre for Research in Neurosciences, McGill University, 1650 Cedar Avenue (L7-224), Montréal, Québec, Canada, H3G 1A4Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montréal, Québec, Canada, H3A 2B4Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montréal, Québec, Canada, H3A 2B4Centre Hospitalier Affilié Universitaire de Québec and the Hôpital de l'enfant-Jésus, Département des Sciences neurologiques, Québec, Québec, Canada, G1J 1Z4Centre de recherche du CHUM, Hôpital Notre-Dame, Université de Montréal, Montréal, Québec, Canada, H3L 1K5McGill University Health Center Research Institute and the Centre for Research in Neurosciences, McGill University, 1650 Cedar Avenue (L7-224), Montréal, Québec, Canada, H3G 1A4; Corresponding author. G. A. R. Centre for Research in Neurosciences, McGill University, and the Montreal General Hospital, 1650 Cedar Avenue (L7-224), Montréal, Québec, Canada, H3G 1A4. Fax: +1 514 934 8265.Oculopharyngeal muscular dystrophy (OPMD) is a late-onset disorder caused by a (GCG)n trinucleotide repeat expansion in the poly(A) binding protein nuclear-1 (PABPN1) gene, which in turn leads to an expanded polyalanine tract in the protein. We generated transgenic mice expressing either the wild type or the expanded form of human PABPN1, and transgenic animals with the expanded form showed clear signs of abnormal limb clasping, muscle weakness, coordination deficits, and peripheral nerves alterations. Analysis of mitotic and postmitotic tissues in those transgenic animals revealed ubiquitinated PABPN1-positive intranuclear inclusions (INIs) in neuronal cells. This latter observation led us to test and confirm the presence of similar INIs in postmortem brain sections from an OPMD patient. Our results indicate that expanded PABPN1, presumably via the toxic effects of its polyalanine tract, can lead to inclusion formation and neurodegeneration in both the mouse and the human.http://www.sciencedirect.com/science/article/pii/S096999610400227XOPMDDystrophyCNSTransgenic micePABPN1Nuclear inclusions |
| spellingShingle | Patrick Dion Vijayalakshmi Shanmugam Claudia Gaspar Christiane Messaed Inge Meijer André Toulouse Janet Laganiere Julie Roussel Daniel Rochefort Simon Laganiere Carol Allen George Karpati Jean-Pierre Bouchard Bernard Brais Guy A. Rouleau Transgenic expression of an expanded (GCG)13 repeat PABPN1 leads to weakness and coordination defects in mice Neurobiology of Disease OPMD Dystrophy CNS Transgenic mice PABPN1 Nuclear inclusions |
| title | Transgenic expression of an expanded (GCG)13 repeat PABPN1 leads to weakness and coordination defects in mice |
| title_full | Transgenic expression of an expanded (GCG)13 repeat PABPN1 leads to weakness and coordination defects in mice |
| title_fullStr | Transgenic expression of an expanded (GCG)13 repeat PABPN1 leads to weakness and coordination defects in mice |
| title_full_unstemmed | Transgenic expression of an expanded (GCG)13 repeat PABPN1 leads to weakness and coordination defects in mice |
| title_short | Transgenic expression of an expanded (GCG)13 repeat PABPN1 leads to weakness and coordination defects in mice |
| title_sort | transgenic expression of an expanded gcg 13 repeat pabpn1 leads to weakness and coordination defects in mice |
| topic | OPMD Dystrophy CNS Transgenic mice PABPN1 Nuclear inclusions |
| url | http://www.sciencedirect.com/science/article/pii/S096999610400227X |
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