Modelling the pathogenesis of X-linked distal hereditary motor neuropathy using patient-derived iPSCs [RESEARCH ARTICLE]

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.

Source: DMM Disease Models and Mechanisms - January 12, 2020 Category: Biomedical Science Authors: Perez-Siles, G., Cutrupi, A., Ellis, M., Kuriakose, J., La Fontaine, S., Mao, D., Uesugi, M., Takata, R. I., Speck-Martins, C. E., Nicholson, G., Kennerson, M. L. Tags: Stem Cells, Neuromuscular RESEARCH ARTICLE Source Type: research