FIGURE 2.

De novo expression of sdk-1 specifically in podocytes in vivo leads to FSGS. A, double transgenic mice (carrying both podocin-Cre and floxed sdk-1 transgenes) express sdk-1 specifically in podocytes as determined by immunostaining. B, monthly urine dipstick measurements were recorded for double transgenic (n = 22), podocin-Cre alone (n = 5) and floxed sdk-1 alone (n = 5) mice for a total of 1 year. Double transgenic mice begin to develop overt proteinuria at an age of 5 months as compared with single transgenic littermates that did not become proteinuric. Mice were considered proteinuric for a dipstick reading of 2+ or greater that persisted for 2 consecutive months or if an animal expired spontaneously after a single positive reading before a second reading could be performed. C, at 9 months of age, double transgenic mice were sacrificed, and kidneys were harvested for routine pathology. Periodic acid-Schiff staining demonstrates protein casts and tubular protein resorption droplets (upper left, 20×), classic FSGS lesions (upper right, 60×), glomerulus with collapse and epithelial cell proliferation with pseudocrescent (lower left), and a globally sclerotic glomerulus (lower right). D, electron microscopy shows severe foot process effacement with condensation of actin filaments above the glomerular basement membrane, and focal cytoplasmic vacuolization. E, urine albumin:creatinine ratios shows massive proteinuria in double transgenic animals as compared with single transgenic littermates. Error bars indicate S.E.