Kidney phenotype of NMII-A mutant mice. (A) Representative glomeruli from mutant mice show various stages of glomerulosclerosis in both heterozygous and homozygous glomeruli from segmental (Avi) to more nearly global (Aii-v). PAS-stained sections. Ages and sexes are (Ai) 9-month and female, (Aii) 6-month female, (Aiii) 12-month female, (Aiv) 12-month male, (Av) 9-month female, and (Avi) 7-month male. (B) Bar graph showing albumin/creatinine ratios in urine from mutant and A⁺/A⁺ mice. All the mutant mouse lines show increased albumin excretion (13 of 44 for A^R702C/A⁺, 11 of 28 for the A^D1424N/A⁺, and 4 of 11 for the A^E1841K/A⁺) compared with A⁺/A⁺ mice. *P = .044, 1-way ANOVA, mean ± SEM. (C) Immunofluorescence confocal images of A^gfp/A⁺ and A^gfpR702C/A⁺ kidney glomeruli stained with anti-GFP (green) and anti-synaptopodin (red) showing localization of NMII-A in the podocytes. DAPI (blue) stains nuclei. Bar, 20 μm. (D) Transmission EM showing podocyte foot process effacement (arrow) in A^D1424N/A^D1424N glomerulus compared with A⁺/A⁺ foot processes. Scanning (Ei-ii) and transmission (Eiii-iv) EM images of A⁺/A⁺ cre⁺ and A^pod/A^pod glomeruli. The A^pod/A^pod podocytes are notable for shortened primary and secondary processes and reduced numbers of foot processes and filtration slits between the foot processes. Foot process widths (arbitrary units) were measured from the transmission EM obtained from 1 mouse of each genotype with the use of ImageJ (NIH): A⁺/A⁺ cre⁺: 0.105 ± 0.06, n = 371; and A^pod/A^pod: 0.319 ± 0.35, n = 293. GBM indicates glomerular basement membrane.