p27Kip1 knockout mice are protected from diabetic nephropathy: Evidence for p27Kip1 haplotype insufficiency1

Deletion of p27Kip1 attenuates the functional and morphologic features of diabetic nephropathy. Although deletion of p27Kip1 abolished some parameters of diabetic glomerular hypertrophy, the significant reduction of TGF-β1 expression in the tubulointerstitium indicates that other protective mechanisms could be operative. The p27Kip1 gene is haplo-insufficient because diabetic p27Kip1 +/- mice exhibited an intermediate degree of functional and structural renal injury. Our data shows that p27Kip1 plays an important role in diabetic nephropathy.