Figure 2.

Histologic changes in proximal tubule-specific autophagy-deficient mice. (A) PAS-stained kidney cortex from 3-week-old, 8-week-old, 6-month-old, and 9-month-oldAtg5^flox/flox; KAP-Cre⁻ (left) and Atg5^flox/flox; KAP-Cre⁺ (right) mice (n = 4 to 5). Atg5^flox/flox; KAP-Cre⁺ mice exhibited slight hypertrophy of the tubular cells at 8 weeks and accumulation of cytosolic amorphous substrates at 6 months. Arrows indicate tubular cells with cytosolic accumulation of amorphous substrates. Bars, 50 and 20 μm (insets). (B) Immunostaining of megalin, a marker of the proximal tubular brush border, showed that the hypertrophied cells (8 weeks) and amorphous substrates-accumulated cells (9 months) are proximal tubular cells in Atg5^flox/flox; KAP-Cre⁺ mice (n = 5). Bar, 20 μm. (C–E) Atg5 deficiency causes accumulation of crescent-like structures and deformed mitochondria. Electron micrographs of kidney proximal tubules from Atg5^flox/flox; KAP-Cre⁻ (C and E) and Atg5^flox/flox; KAP-Cre⁺ (D, F, and G) mice of 8 weeks (C and D) and 9 months (E through G) of age. The autophagy-deficient proximal tubular cells showed accumulation of crescent-like structures in 8-week-old (D) and 9-month-old (F) mice. (G) The autophagy-deficient proximal tubular cells of 9-month-old mice also contained deformed mitochondria. The figure is a representative of multiple experiments (n = 3). Bars, 2 μm (C–F) and 500 nm (insets of C–F and G). Magnification, ×400 (A), ×1000 (insets of A and B), ×2500 (C through F), and ×10,000 (insets of C–F and G).