Proliferation of nephron progenitor cells (NPC) is essential to maintain and expand the progenitor pool during kidney development. Proliferation depends on mitochondrial aspartate biosynthesis to fuel nucleotide synthesis. Glutamic-Oxaloacetic Transaminase 2 (GOT2) is a mitochondrial enzyme that catalyzes the transamination of glutamate and oxaloacetate to form aspartate and α-ketoglutarate. While GOT2 is essential for nucleotide synthesis and proliferation in cancer cells, the role of GOT2 during kidney development is unknown. Using publicly available scRNAseq datasets and immunofluorescence (IF) staining, we show Got2 is broadly expressed during kidney development. To determine the necessity of GOT2 we took a genetic approach to knockout a conditional (floxed – fl) Got2 allele in NPC using Six2Cre. Western blot and qPCR analyses of newborn mice confirmed efficient ablation of Got2 using this approach. Histology and gross analyses found that Six2Cre;Got2fl/fl mice have smaller kidneys at birth. IF staining using both anti-Six2 and anti-Pax2 found a reduction in the size of the NPC population in Six2Cre;Got2fl/fl mice compared to Six2Cre;Got2fl/+ littermate controls. Our findings suggest that GOT2 is essential to maintain and/or expand the NPC population. In light of these findings, future studies evaluating the effects of Got2 ablation on proliferation and apoptosis are warranted.
