Figure 4

Loss of CORO2B does not impair glomerular function, but influences stress response to Doxorubicin treatment. (a) Schematic illustrating strategy for Coro2b knockout generation by deletion of Exon 4–9. (b,c) Coro2b knockout was confirmed by western blotting of isolated podocytes and immunofluorescence staining of kidney cryo-sections. The slit-diaphragm component NEPHRIN was used to co-label the podocyte compartment. (e) Albumin to creatinine ratio (ACR) indicates normal glomerular function in Coro2b knockout animals up to 9 months. (Individual animals were indicated as dots.) (f–i) 12 months old Coro2b knockout animals showing normal glomerular histology in PAS staining as well as normal expression and localization of the slit diaphragm component NEPHRIN and the podocyte specific actin cytoskeleton protein SYNPO. (j) Coro2b knockout mice exhibit increased resistance to Doxorubicin induced podocyte damage, indicated by higher ACR in wild type animals after 3 and 5 weeks of treatment. (5 WT and 7 KO animals were analyzed at indicated time points, for measurement after 5 weeks of treatment an additional experimental run of 3 WT and 5 KO animals was included; *p < 0.05, **p < 0.01; for detailed information see statistical section) (k–n) PAS staining and immunofluorescence staining for NEPHRIN and SYNPO of Doxorubicin treated animals reveals modest mesangial expansion and decreased levels of bona fide podocyte markers in wild type mice.