Figure 4.
MYH9 E1841K mutation results in poor survival and severe FSGS in the subtotal nephrectomy model. (A) Mean of means for SBP at fifth week and eighth week. After 2 weeks of training, SBP was recorded daily during each specific week and averaged. Mean of means for SBP at fifth week (mm Hg): MYH9 +/+ (n=4) 150.2±12.1, MYH9 +/E1841K (n=4) 135.9±4.9, MYH9E1841K/E1841K (n=3) 162.3±9.2; at eighth week: MYH9 +/+ (n=4) 174.6±7.4, MYH9 +/E1841K (n=4) 154.1±8.8, MYH9E1841K/E1841K (n=1) 180.3. Insert shows differences between mean SBP at fifth and eighth week after Nx. P=NS among groups (ANOVA). Two moribund MYH9E1841K/E1841K mice were euthanized during the sixth and seventh week after Nx, and therefore their SBP could not be obtained, but their kidneys were preserved for histopathology scores which are included in the analysis below. (B) A/C ratio (log scale) for each individual mouse for 24-hour urine collected at the end of the eighth week after Nx is shown. Mean urinary A/C ratio (µg/mg): MYH9 +/+ 612.2±103, MYH9 +/E1841K 224.1±132.5, and one MYH9E1841K/E1841K mouse 1671.3. (C) Periodic acid–Shiff staining of kidney sections (40×) after subtotal Nx: MYH9 +/+ mice and MYH9 +/E1841K mice have similar moderate degree of FSGS, whereas MYH9 E1841K/E1841K have severe segmental to near global sclerosis in virtually all glomeruli. Black scale bar=50 µm. (D) Total pathology score is shown for each individual mouse. Two MYH9E1841K/E1841K mice euthanized earlier during the sixth and seventh week after Nx are included in the graph and in the calculation of means of total kidney pathology scores for each group of mice. MYH9 +/+ (n=4) 29.0±3.0, MYH9 +/E1841K (n=4) 19.8±2.8, and MYH9E1841K/E1841K (n=3) 32.7±4.3; P=0.06 (by ANOVA). Table shows kidney pathology scores for glomerular, tubular, and interstitial injuries in the chronic kidney model (after subtotal Nx). See description in Figure 2F above for pathologic features assessed.