ER morphological alterations induced by NP1 mutants are detected by transmission electron microscopy. For each condition, pictures representative of the characteristic observations are included. ER is indicated by arrows, mitochondria by arrowheads, lysosomes by asterisks. (A and B) Electron microscopy of non-transfected COS7 cells showed normal development of endoplasmic reticulum and mitochondria at low (A) and high magnification (B). (C and D) COS7 cells transfected with the wild-type NP1 plasmid. No modification of cellular organelles was observed at low (C) or high (D) magnification. (E and F) COS7 cells transfected with the p.E327G mutant plasmid showed a single juxtanuclear cluster of ER (E, black and white arrowheads). On high magnification (F), ER cisternae intermingled with some lysosomes and multilamellar bodies (curved arrow). (G and H) COS7 cells transfected with the p.G389R mutant plasmid. The ER cisternae were diffusely distributed in the cytoplasm around the nucleus (G). On high magnification (H), ER cisternae appeared swollen and mingled with some lysosomes, as observed for the p.E327G variant.