Extended Data Fig. 5: Pathogenic mutations accumulate in other two mouse models with aging.
a, NBTx staining of whole kidney sections from 75-week-old control and TrnE high-mutant mice. b, NBTx staining of different areas (renal cortex, outer medulla, and inner medulla) of kidney sections from 75-week-old control and TrnE high-mutant groups. Damage varied from the renal cortex to the medulla. c, Percentage of NBT positive blue area in kidney sections from 50-week-old and 75-week-old TrnE high-mutant males and females (mean ± SD, n = 14 (50w) and n = 16 (75w) in males, n = 25 (50w) and n = 15 (75w) in females). d, mtDNA copy number quantification in bulk kidney from control and TrnE high-mutant mice at different ages (8, 50, and 75 weeks) (mean ± SEM, n = 3–4 per group. Unpaired two-tailed Student’s t-test, ** P < 0.01). e, f, Kidney mutation load in mutant TrnA (e) and mutant TrnK (f) mice over time (8, 24, 50, and 100 weeks). The black line represents the line of best fit with 95% confidence intervals (gray). (mean ± SEM, n = 3 (8w, 24w), n = 7–8 (50w) and n = 5–7 (100w)). g, Kidney morphology from 100-week-old mice with WT, high TrnA, and high TrnK mutations. Scale bar = 5 mm. h, NBTx staining of kidney sections from 24-week-old WT, TrnA, and TrnK high-mutant mice. Cells with normal COX activity do not retain NBT, while those with COX deficiency appear blue. (section thickness = 10 μm) i, Transmission electron microscopy (TEM) images of mitochondria from the kidney epithelial cells of 100-week-old WT, TrnA, and TrnK high-mutant mice.
