Increase in podocyte number induced by SV40T antigen during the fetal stage does not expand glomerular size in mice

In healthy kidneys without injury or compensatory hypertrophy, glomerular volume generally correlates with the podocyte number. In this study, we investigated whether experimentally increasing podocyte numbers can expand glomerular volume. We generated transgenic mice in which the SV40 large T antigen (SV40T) was selectively expressed in podocytes in a doxycycline-inducible manner. In adult mice, doxycycline treatment successfully induced cell cycle re-entry in podocytes, albeit with low efficiency. However, prolonged treatment caused proteinuria and podocyte injury. When doxycycline was administered during embryogenesis, newborn mice clearly exhibited an increase in podocyte proliferation, leading to an average of 54% increase in podocyte number. These additional podocytes frequently formed multiple layers and detached into Bowman's space or tubular lumen; consequently, the glomerular tuft area did not increase. By postnatal Day 7, excess podocytes disappeared, and podocyte counts returned to levels comparable to those in control mice. These findings indicate that glomerular volume is determined at or before the S-shaped body stage, and that forced increases in podocyte number induced by SV40T at later developmental stages are insufficient to expand glomerular volume.