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. 2018 Jan 4;9:70. doi: 10.1038/s41467-017-01859-9

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 8 — Inactivation of Twinkle in astrocytes leads to brain vacuolization and spongiotic encephalopathy. a Cortical morphology with hematoxylin/eosin staining from terminal stage of TwKO^astro and TwKO^neuro mice. Representative images of the brain mid-sagittal sections. Extensive brain vacuolization in TwKO^astro indicated with arrows. b Spongiotic encephalopathy of TwKO^astro has progressive nature. Brain graphs show the affected regions with severity of pathology demonstrated with intensity of the color shading. c Vacuoles (blue arrows) and astrocyte nuclei (black arrows) in hematoxylin/eosin staining. d Immunohistochemistry of GFAP in TwKO^astro and vacuoles enwrapped by an astrocyte (blue arrow). e Representative electron micrograph of vacuoles. Upper arrow indicates a vacuolated mitochondrion, lower arrow indicates group of vacuoles in the brain of TwKO^astro. f Representative electron micrograph of vacuolated myelinated axon. Brain graph shows sampling site. Scale bars: 100 μm (a, b); 10 μm (c), 5 μm (d). g Time-course development of brain pathology in TwKO^astro and TwKO^neuro mice