Chondrocytes of wild-type controls and untreated Tg197 mice. (a) Wild-type control at age 8 weeks: nucleus (N), plasma membrane with short cytoplasmic protrusions (arrow), rough endoplasmic reticulum (r-ER) (arrowhead), and mitochondria (m); (b) untreated Tg197 mouse at age 4 weeks: nucleus (N) and plasma membrane with cytoplasmic thin protrusions (arrow) appear normal, while the cytoplasm shows vacuoles (v) with granular materials inside (double arrow) and dilated cisternae (arrowhead). (c-f) Untreated Tg197 mouse at age 8 weeks: degenerating chondrocytes showing the following: (c) transparent cytoplasm with nucleus (N) and an accumulation of intracytoplasmic filaments (f), vacuoles (v) and mitochondria (m) with distorted cristae; (d) greatly vacuolated cytoplasm (v), and pyknotic nuclei (N) with cytoplasmic projections coming apart from the cell (arrow); (e) cell organelles from disintegrated cells (o), mitochondria (m), bundles of densely packed collagen fibres (arrowhead), small residues of intermediate filaments (f), and broken cellular processes (arrow); (f) swollen and disrupted r-ER, and bundles of thickened intermediate filaments (f). Basement membrane, cytoplasmic organelles (arrow), and cellular processes (arrowhead) were also fragmented. Electron-dense areas (e) are seen in the intercellular matrix. N = 4 joints; mean percentage of degenerating chondrocytes = 40% and 80% of total at 4 and 8 weeks of age, respectively. Bars = 2 μm.