Figure 3
From: MDM2 prevents spontaneous tubular epithelial cell death and acute kidney injury
Tubular cell-specific MDM2 knockout in mouse model results in acute kidney injury with fast decline of renal function. (a) Mice expressing inducible cre recombinase under control of Pax8 promoter were crossed with MDM2fl/flmice to generate tubular cell-specific MDM2 knockout mice. (b) RT-PCR analysis confirmed suppression of MDM2 mRNA expression in kidney lysates of Pax8rtTA-cre;MDM2f/f mice treated with doxycycline. (c) Immunohistochemical staining confirmed MDM2 deletion in tubular cells while in podocytes in glomerulus the MDM2 expression remained unchanged. (d) Pax8rtTA-cre;MDM2f/f mice treated with doxycycline developed increasing elevation of plasma creatinine and plasma BUN (n=5–6 mice in each group). (e) Left: GFR measurement showed significant decrease of GFR from day 6 of doxycycline treatment in Pax8rtTA-cre;MDM2f/f mice while the GFR of control MDM2f/f mice was unaffected. Right: Kaplan–Meyer survival curve of MDM2−/−tubulus and control mice (n=17 per group). (f) mRNA expression of p53 as well as of tubules damage markers KIM-1, NGAL and TIMP-2 was increasingly elevated in MDM2−/−tubulus mice kidneys in comparison to control mice kidneys. Data are means±S.E.M. *P<0.05, **P<0.01, ***P<0.005
