Fig. 5
From: Combined loss of LAP1B and LAP1C results in an early onset multisystemic nuclear envelopathy
Patient cell nuclei contain intricate channels with trapped cytoplasmic organelles. Control (a) and patient-derived primary fibroblasts (b, c) were prepared for transmission electron microscopy as described in Methods. Dashed red and blue lines indicate areas enlarged in subsequent panels. Side views were obtained by the fixation of attached cells followed by scraping off the surface and further fixation, embedding, and preparation of thin sections. Top views were obtained by a different preparation protocol, in which cells were fixed and embedded directly on a coverslip surface, to ensure an identical flat orientation of all the cells. a Side and top views of control fibroblasts exhibiting normal nuclear morphology and no cytoplasmic channels. Enlarged areas show the two nuclear membranes, the perinuclear space, and nuclear pore complexes in cross-section. b Side and top views of patient-derived fibroblasts. In the side view, a cytoplasmic channel transects the flat nucleus from top to bottom. Note cytoplasmic organelles near the top opening of the channel. The top view shows a single cell containing an intricate, irregularly shaped channel, which is fully encompassed by a double membraned nuclear envelope. Double membranes and a typical nuclear pore in cross-section (arrow) can be identified in the bottom left panel. Arrowheads point to trapped cytoplasmic organelles. c Additional top view images from a different patient-derived fibroblast. Note several smaller suspected channels, seen in cross-section and clearly encompassed by double nuclear membranes. Scale bars: black 2 µm, red 400 nm
