LRRK2 KO mice develop degeneration in the kidney from an early age. (a) Comparison of perfused kidneys extracted from WT, HET and KO mice at 3, 6, 12 and 20 months of age. Coloration changes were observed as early as 3 months in KO mice. HET kidneys were not affected. (b) Histopathology of kidney reveals morphological changes. H&E at 3 months shows pigmentation in proximal tubule (arrow). H&E at 18 months shows extensive vacuolization (white arrow) and pigmentation (arrowhead). Positive p62 staining can be seen at 3 months in KO and is extensive by 18 months. Pigmentation in tubules, most likely to be lipofuscin, is autofluorescent in rhodamine channel at both 3 and 18 months in KO. Scale bar is 50 microns. (c) Electron microscopy in KO kidney reveals degenerative changes at the ultrastructural level in renal cortex tubular epithelial cells from 18 month old KO mouse. (i) Normal epithelial cell in WT mouse. (N) nucleus. (ii) Degenerating debris (d) in tubular epithelial cell in KO. (iii) Higher power image from KO showing normal mitochondria (M), lipid (Lp) probably lipofuscin and degenerative structure, probably lysosomal-containing lipid. (iv) Higher power image from KO of degenerative structure showing extensive debris.