Figure 2
Mouse model B. Pax8-driven excision of Vps34 exon 21 (Pax8-Vps 34Δ/Δ) causes delayed postnatal kidney lesions and death. (a) Survival, growth and phenotype. In this mouse model, Vps34Δ/Δ pups are born at the expected Mendelian frequency and gain weight normally until ~P14 (weaning), then level off until death. Picture shows a typical appearance at P21. Vps34Δ/Δ pups are distinctly smaller but appear otherwise normal. They exhibit marked polyuria. (b) Western blotting of urine (n = 4 WT; 5 Vps34Δ/Δ), collected by bladder punction at sacrifice (P7) or upon 6-h placement in adapted metabolic cage (P14), for transferrin (TR), albumin (ALB) and vitamin D-binding protein (DBP). Loading was normalized for equal creatinine content. Positions of corresponding protein signals (in kDa) are indicated at the right. Low molecular-weight proteinuria is found in Vps34Δ/Δ samples. At the right, intensity of albuminuria at P14 was compared to urinary loss of IgG, both quantified by reference to serial dilutions of normal mice plasma, and IgG/albumin molar ratio was calculated as index of selective proteinuria. (c) Histology after PAS staining. Strong apical PAS stain is observed in all WT PTCs (arrowhead), contrasting with paler Vps34Δ/Δ pups PTCs at P7 and marked vacuolization at P14 (arrows).
