List of published iPSC-derived lines modelling CMT
| CMT subtype | New classification | Genetic mutation | Starting material | Cell line type | Mode of generation | Phenotypes | Mechanisms | References |
| CMT1A | AD-CMTde-PMP22 | PMP22 duplication | Fibroblast | iPSC, pN, NCSC, Schwann cells | Retroviral vectors expressing OCT4, SOX2, KFL4 and C-MYC | Schwann cell developmental defect | Developmental disabilities of Schwann cells, RNA sequencing hinting towards dysregulation of cholesterol synthesis, autophagy, PTEN,ERK/MAPK and EPHRIN receptor signalling | s28 |
| CMT1A | AD-CMTde-PMP22 | PMP22 duplication | na | iPSC, NCSC | na | na | Global gene expression analysis | s27 |
| CMT2A | AD-CMTax-MFN2 |
R364W_
MFN2 | Fibroblast | iPSC, sMN | Retroviral vectors expressing SOX2, OCT3/4, KFL4 and C-MYC | Mitochondria moved at slower anterograde and retrograde velocities, hyperexcitable motor neurons and altered sodium and calcium channel dynamics | Increased neuronal firing possibly due to Na+/K+pump failure | s21 |
| CMT2E | AD-CMTax-NEFL | N98S_NEFL | Fibroblast | iPSC, sMN | Retroviral vectors expressing SOX2, OCT3/4, KFL4 and C-MYC | Increased accumulation of NEFL in the perikarya of neurons, mitochondria travelled shorter distances at slower velocities, hyperexcitable motor neurons and altered sodium and calcium channel dynamics | Impaired mitochondrial trafficking, increased neuronal firing possibly due to Na+/K+pump failure | s21 |
| CMT2F and dHMN-IIB | AD-CMTax-HSPB1 | S135F, P182L_HSPB1 | Fibroblast | iPSC, MN | Sendai virus- vectors, expressing SOX2, OCT4,KLF4, and c-MYC | Less moving mitochondria, Reduced absolute velocity of mitochondria | Defects in mitochondrial transport, reduced α-tubulin acetylation | s25 |
| CMT2A,CMT2E, CMT2F, CMT2L | AD-CMTax-MFN2, AD-CMTax-NEFL, AD-CMTax/dHMNax-HSPB1, AD-CMTax-HSPB8 | R94Q_MFN2, P8R_NEFL, K141N_HSPB8_and G84R_HSPB1 | Fibroblast | iPSC, sMN | Sendai virus- vectors, expressing SOX2, OCT3/4,KLF4and c-MYC | – | Reduced PFN2 expression in R94Q_MFN2, P8R_NEFL sMN lines | s22 |
| Demyelinating neuropathies: (CMT1A, CMT1B and CMT1D) | AD-CMTde-PMP22, AD-CMTde-MPZ, AD-CMTde-EGR2 |
PMP22
Duplication, R98C_ MPZ, R353G_ EGR2 | PBMC | iPSCs, NCSC | Episomal vectors encoding OCT3/4, SOX2, KLF4, L-MYC, LIN28 and p53 | Global gene expression, analysis of NCSC- glutathione-mediated detoxification pathway as common pathway behind demyelinating neuropathies | s29 | |
| CMTX | XL-CMTin-GJB | V139M_GJB1 | Fibroblast | iPSC | Episomal vectors encoding OCT4, SOX2, KLF4, L-MYC, LIN28 and shRNA-p53 | – | – | s95 |
| CMT1F | AR-CMTde-NEFL | A367*_NEFL | Fibroblast | iPSC | Episomal, retroviral and Sendai viral vectors encoding OCT4, SOX2, KLF4 and MYC | Complete absence of NEFL protein | Altered Intermediate filament transcript dynamics | s96 |
*Nonsense mutation.
iPSCs, induced pluripotent stem cells; MN, motor neuron; na, not available; NCSC, neural crest stem cells, progenitor of Schwann cells; PBMCs, peripheral blood mononuclear cells; pN, peripheral neurons; sMN, spinal motor neurons.
NCSC, neuronal crest stem cells.