PMP22 OVEREXPRESSION CAUSES LIPID RECYCLING DEFECTS THAT ALTERS THE PLASMA MEMBRANE IN CMT1A

Abstract

Intro (50 words) Duplication of the peripheral myelin protein 22 (PMP22) causes Charcot-Marie-Tooth disease 1A (CMT1A) and is known to dysregulate lipid metabolism. However, a lack knowledge persists in the underlying mechanisms that lead to lipid metabolic defects that ultimately give rise to the CMT1A phenotype. Methods (50 words) We performed bulk RNA-sequencing on sciatic nerves of the C3 and C22 CMT1A mouse models (3-12 weeks of age) and on CMT1A patient derived Schwann cell precursors differentiated from induced pluripotent stem cells (iPS-SCPs). LC-MS/MS lipidomic analysis was also performed on 5-week-old C3 mice and on CMT1A iPS-SCPs. The lipidomic phenotypes were further analysed via electron microscopy, flow cytometry, high-content confocal immunofluorescence imaging and western blot. Results (100 words +-)