Modelling the pathogenesis of X-linked distal hereditary motor neuropathy using patient-derived iPSCs
| Autor: | 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 |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Disease Models & Mechanisms, Vol 13, Iss 2 (2020) |
| Druh dokumentu: | article |
| ISSN: | 1754-8403 1754-8411 |
| DOI: | 10.1242/dmm.041541 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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