The 5/6 Nx + DOCA-salt model induces glomerular lesions characteristic of focal and segmental glomerulosclerosis. (A) Schematic of the experimental set-up. After 14 days of treatment with doxycycline (dox) to induce the irreversible genetic labeling and a washout phase of 7 days, a subtotal nephrectomy (5/6) was performed. After a recovery phase, two 25-mg DOCA pellets were implanted subcutaneously (arrows) and 0.1 to 0.9% NaCl was added to the drinking water. Animals were killed after 12 weeks (asterisk). (B through F) PAS-stained paraffin section showing segmental glomerulosclerosis induced in the 5/6 Nx + DOCA-salt model. (B) Lesion near the vascular stalk, where two adhesions (arrowheads), segmental sclerosis (asterisks), a thickened BC (arrow with tails), and vacuolization of podocytes (arrow), is present. (C,D,F) Glomerular lesions with extracapillary proliferations (arrowheads) were also observed. Thickening of the basement membrane of BC (arrow with tails) was observed, mostly in association with an adhesion (B, arrowheads) and/or segmental sclerosis of the glomerular tuft (asterisk). (D and F) More advanced sclerotic lesions (asterisk).