Heterozygous expression of Cre recombinase in podocytes has no impact on the anti-glomerular basement membrane glomerulonephritis model in C57BL/6J mice

A recent article described a thickening of the glomerular basement membrane (GBM) along with changes in the expression of key components of the extracellular matrix in 6-month-old NPHS2-Cre transgenic mice, which express the Cre recombinase specifically in podocytes. This transgenic line has been widely used to characterize the implication of candidate genes in glomerular diseases in younger mice. Using a different mouse strain (C57BL/6J) than the previous report (129S6/SvEvTac), we sought to characterize 3- and 6-month-old NPHS2-Cre^+/- mice in control and pathological conditions. At baseline, there was no difference in renal function and histology between control and NPHS2-Cre^+/- mice. Notably, GBM thickness evaluated by transmission electron microscopy was similar between the two groups. We then induced an immune-mediated severe glomerular insult, the anti-glomerular basement membrane glomerulonephritis model (anti-GBM-GN) in 3-month-old control and NPHS2-Cre^+/- mice. NPHS2-Cre^+/- mice exhibited the same alterations in renal function and structure as control mice. In summary, our study strongly suggests that NPHS2-Cre^+/- transgenic mice on a C57BL/6J background can be safely used for podocyte-specific gene inactivation in control conditions and in the anti-GBM-GN model.