Figure 2
From: Clr-f expression regulates kidney immune and metabolic homeostasis
Clr-f-deficient mice exhibit kidney pathology and altered kidney function. (A) Renal tissue sections from 12-week-old WT and Clr-f−/− mice (n = 4) stained with PAS. Upper panels show the appearance of lesions in proximal and distal tubules of Clr-f−/− mice with severity ranging from minimal epithelial disturbance (not shown), (I) flattened tubular epithelium with numerous cytoplasmic vacuoles (arrows), nuclear apical displacement, and (II) moderate and aggravated lesions with the disappearance of tubular epithelium. The green arrowhead in the far right panel (II) indicates an area of cell loss where the tubular basement membrane is covered by a thin layer of cytoplasm. Arrows indicate detached cells in tubular lumina and the asterisk marks an area of accumulated necrotic debris and loss of epithelial cell brush border. Lower panels show glomerular sections from 12-week-old WT and Clr-f−/− mice (n = 4) stained with PAS. Clr-f−/− mice exhibit a varying extent of glomerular mesangiolysis with (I) primary phase and (II) fragmentation and pronounced disruption of glomeruli. Arrows indicate capillary aneurysms (arrow). An asterisk indicates necrotizing cellular debris and plasma in Bowman’s spaces. (B) Pathology scoring of the observed glomerular lesions. Scores are based on the level of disappearance of the glomerulus: 0: < 10%, 1: 10–30%, 2: 30–60%, 3: > 60%. The bubble area represents the proportion of total counts (****P ≤ 0.0001). (C) Transmission electron micrographs demonstrate severe podocyte destruction and podocyte foot process effacement in Clr-f−/− mice (red arrows). The inset boxes in the upper panels are shown in the lower panels. Yellow arrowheads indicate GBM thickening, green arrowheads indicate subendothelial electron-dense deposits, blue arrowhead indicates mitochondrial cristolysis. Upper panel scale bars represent 2 μm. The lower left and middle panel scale bars represent 800 nm and lower right panel scale bar represents 500 nm. (D) Measurements of GBM thickness from electron microscopy micrographs of WT (n = 2) mice and Clr-f−/− (n = 3) mice. Each point represents a distinct GBM measurement. (****P ≤ 0.0001). (E) IF staining of WT and Clr-f−/− glomerular sections for IgA, IgM, IgG deposition, and (F) C3 complement protein in 12-week-old mouse kidneys. Scale bars represent 40 μm. (G) Protein and creatinine measurements in urine and serum samples and urinary fractional excretion of sodium (FENa) values from 12-week-old male Clr-f−/− and WT mice. (H) Blood pressure measurement in Clr-f−/− mice compared to their WT littermates at indicated ages. Mean and standard deviation are shown.
