Modelling the pathogenesis of X-linked distal hereditary motor neuropathy using patient-derived iPSCs
ATP7A encodes a copper-transporting P-type ATPase and is one of 23 genes in which mutations produce distal hereditary motor neuropathy (dHMN), a group of diseases characterized by length-dependent axonal degeneration of motor neurons. We have generated induced pluripotent stem cell (iPSC)-derived mo...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2020-02-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/13/2/dmm041541 |
| _version_ | 1828486069672214528 |
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| author | Gonzalo Perez-Siles Anthony Cutrupi Melina Ellis Jakob Kuriakose Sharon La Fontaine Di Mao Motonari Uesugi Reinaldo I. Takata Carlos E. Speck-Martins Garth Nicholson Marina L. Kennerson Annemieke Aartsma-Rus James Dowling Maaike van Putten |
| author_facet | Gonzalo Perez-Siles Anthony Cutrupi Melina Ellis Jakob Kuriakose Sharon La Fontaine Di Mao Motonari Uesugi Reinaldo I. Takata Carlos E. Speck-Martins Garth Nicholson Marina L. Kennerson Annemieke Aartsma-Rus James Dowling Maaike van Putten |
| author_sort | Gonzalo Perez-Siles |
| collection | DOAJ |
| description | ATP7A encodes a copper-transporting P-type ATPase and is one of 23 genes in which mutations produce distal hereditary motor neuropathy (dHMN), a group of diseases characterized by length-dependent axonal degeneration of motor neurons. We have generated induced pluripotent stem cell (iPSC)-derived motor neurons from a patient with the p.T994I ATP7A gene mutation as an in vitro model for X-linked dHMN (dHMNX). Patient motor neurons show a marked reduction of ATP7A protein levels in the soma when compared to control motor neurons and failed to upregulate expression of ATP7A under copper-loading conditions. These results recapitulate previous findings obtained in dHMNX patient fibroblasts and in primary cells from a rodent model of dHMNX, indicating that patient iPSC-derived motor neurons will be an important resource for studying the role of copper in the pathogenic processes that lead to axonal degeneration in dHMNX. |
| first_indexed | 2024-12-11T09:26:29Z |
| format | Article |
| id | doaj.art-96cf025b67e84cd9944cad361424728a |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-11T09:26:29Z |
| publishDate | 2020-02-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-96cf025b67e84cd9944cad361424728a2022-12-22T01:13:08ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112020-02-0113210.1242/dmm.041541041541Modelling the pathogenesis of X-linked distal hereditary motor neuropathy using patient-derived iPSCsGonzalo Perez-Siles0Anthony Cutrupi1Melina Ellis2Jakob Kuriakose3Sharon La Fontaine4Di Mao5Motonari Uesugi6Reinaldo I. Takata7Carlos E. Speck-Martins8Garth Nicholson9Marina L. Kennerson10Annemieke Aartsma-RusJames DowlingMaaike van Putten Northcott Neuroscience Laboratory, ANZAC Research Institute, Sydney, 2139 NSW, Australia Northcott Neuroscience Laboratory, ANZAC Research Institute, Sydney, 2139 NSW, Australia Northcott Neuroscience Laboratory, ANZAC Research Institute, Sydney, 2139 NSW, Australia School of Life Sciences, University of Technology Sydney, Sydney, 2007 NSW, Australia Centre for Cellular and Molecular Biology, School of Life and Environmental Sciences, Deakin University, Burwood, 3125 VIC, Australia Institute for Integrated Cell-Material Sciences and Institute for Chemical Research, Kyoto University, Kyoto 606-8302, Japan Institute for Integrated Cell-Material Sciences and Institute for Chemical Research, Kyoto University, Kyoto 606-8302, Japan Sarah Network Rehabilitation Hospitals, Brasilia, 70297-400 DF, Brazil Sarah Network Rehabilitation Hospitals, Brasilia, 70297-400 DF, Brazil Northcott Neuroscience Laboratory, ANZAC Research Institute, Sydney, 2139 NSW, Australia Northcott Neuroscience Laboratory, ANZAC Research Institute, Sydney, 2139 NSW, Australia ATP7A encodes a copper-transporting P-type ATPase and is one of 23 genes in which mutations produce distal hereditary motor neuropathy (dHMN), a group of diseases characterized by length-dependent axonal degeneration of motor neurons. We have generated induced pluripotent stem cell (iPSC)-derived motor neurons from a patient with the p.T994I ATP7A gene mutation as an in vitro model for X-linked dHMN (dHMNX). Patient motor neurons show a marked reduction of ATP7A protein levels in the soma when compared to control motor neurons and failed to upregulate expression of ATP7A under copper-loading conditions. These results recapitulate previous findings obtained in dHMNX patient fibroblasts and in primary cells from a rodent model of dHMNX, indicating that patient iPSC-derived motor neurons will be an important resource for studying the role of copper in the pathogenic processes that lead to axonal degeneration in dHMNX.http://dmm.biologists.org/content/13/2/dmm041541atp7acopperinduced pluripotent stem cellmotor neuronsdhmn |
| spellingShingle | Gonzalo Perez-Siles Anthony Cutrupi Melina Ellis Jakob Kuriakose Sharon La Fontaine Di Mao Motonari Uesugi Reinaldo I. Takata Carlos E. Speck-Martins Garth Nicholson Marina L. Kennerson Annemieke Aartsma-Rus James Dowling Maaike van Putten Modelling the pathogenesis of X-linked distal hereditary motor neuropathy using patient-derived iPSCs Disease Models & Mechanisms atp7a copper induced pluripotent stem cell motor neurons dhmn |
| title | Modelling the pathogenesis of X-linked distal hereditary motor neuropathy using patient-derived iPSCs |
| title_full | Modelling the pathogenesis of X-linked distal hereditary motor neuropathy using patient-derived iPSCs |
| title_fullStr | Modelling the pathogenesis of X-linked distal hereditary motor neuropathy using patient-derived iPSCs |
| title_full_unstemmed | Modelling the pathogenesis of X-linked distal hereditary motor neuropathy using patient-derived iPSCs |
| title_short | Modelling the pathogenesis of X-linked distal hereditary motor neuropathy using patient-derived iPSCs |
| title_sort | modelling the pathogenesis of x linked distal hereditary motor neuropathy using patient derived ipscs |
| topic | atp7a copper induced pluripotent stem cell motor neurons dhmn |
| url | http://dmm.biologists.org/content/13/2/dmm041541 |
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