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Modelling the pathogenesis of X-linked distal hereditary motor neuropathy using patient-derived iPSCs

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Version 2 2024-06-04, 04:43
Version 1 2020-02-06, 12:55
journal contribution
posted on 2024-06-04, 04:43 authored by G Perez-Siles, A Cutrupi, M Ellis, J Kuriakose, Sharon La FontaineSharon La Fontaine, D Mao, M Uesugi, RI Takata, CE Speck-Martins, G Nicholson, ML Kennerson
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.

History

Journal

DMM Disease Models and Mechanisms

Volume

13

Article number

ARTN dmm041541

Pagination

1 - 16

Location

England

ISSN

1754-8403

eISSN

1754-8411

Language

English

Publication classification

C1 Refereed article in a scholarly journal

Issue

2

Publisher

COMPANY BIOLOGISTS LTD