(A) Normal glomeruli (G) and renal tubular structures are observed in the kidneys of WT mice. In Neu1^ΔEx3 kidney, severe accumulation of storage materials is present in the glomerular cells, and in surrounding tubules (black arrowheads), leading to morphological changes. Deformed tubules with vacuolized epithelial cells are also present in the kidney of Neu1^Cx3cr1ΔEx3 mice. Scale bar: 20 μm. (B) A significant loss of nephrons was observed in the kidney cortex of 4-month-old Neu1^ΔEx3 mice. Panels show representative images with nephrons circled, and the graph shows individual values (number of nephrons/regions of interest selected at the same positions from the cortex and multiplied by the kidney weight to account for kidney enlargement occurring in NEU1-deficient mice due to lysosomal storage), means, and SD obtained from 3 WT, 3 Neu1^ΔEx3, and 4 Neu1^Cx3cr1ΔEx3 male and female mice. P values were calculated using 1-way ANOVA with Tukey’s post hoc test. Scale bar: 50 μm. (C) Masson’s trichrome staining reveals collagen deposits (blue) in the tubulointerstitial areas and parietal epithelium of the Bowman’s capsule in Neu1^ΔEx3 mouse characteristic of renal fibrosis. Scale bar: 100 μm. (D) WT mouse kidney have normal morphology and do not present buildup of lysosomal vacuoles in intraglomerular cells (G), proximal tubular cells (PT), distal tubular cells (DT), and cells of collecting ducts (CD). Conversely, the kidney of Neu1^ΔEx3 mice show a prominent accumulation of vacuoles in intraglomerular cells (G), and, presumably, podocytes (yellow arrow). The epithelial cells of DCT and CD exhibit a prominent accumulation of vacuoles. In Neu1^Cx3cr1ΔEx33 mice, both the cortex and medulla were mildly affected. In the cortex, both intraglomerular cells and DT show a moderate accumulation of lysosomal vacuoles. In the medulla, the descending portions of the loop of Henle are normal. PCT, proximal convoluted tubule; DCT, distal convoluted tubule.