BTBR ob/ob mice show distinct mesangial expansion at 14 wks (B) compared to BTBR wild type (A). These mesangial lesions are progressive as shown at 21 wks (C, D) and result in part from mesangiolysis, with lucency and dissolution of the mesangial (C, arrow). The glomerulus in D shows diffuse and focally nodular mesangial sclerosis (arrowhead) and hyalinosis of an arteriole (D, arrow). Compare to human DN in E with characteristic hyalinosis of arteriole (arrow) and nodular sclerosis (arrowhead), and to the limited mesangial change in leptin receptor deficient db/db mice (F), currently the most widely used murine model of DN in Type II diabetes, at 22 weeks. A–F, silver methenamine stain. Modified from Hudkins KL et al. J Am Soc Nephrol. 2010; 21:1533–1542, reprinted with permission.