Modelling the pathogenesis of X-linked distal hereditary motor neuropathy using patient-derived iPSCs.
Dis Model Mech
; 13(2)2020 01 13.
Article
em En
| MEDLINE
| ID: mdl-31969342
ABSTRACT
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Atrofia Muscular Espinal
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Doenças Genéticas Ligadas ao Cromossomo X
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Células-Tronco Pluripotentes Induzidas
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Modelos Biológicos
Tipo de estudo:
Etiology_studies
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Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article