Single nucleus RNA sequencing of mosiac Pax2 and Pax8 mutant proximal tubules

Pax2 and Pax8 are homologous transcription factors required for kidney development and medullary urine concentration. However, their function in proximal tubule homeostasis and response to acute kidney injury is unknown. Mice with proximal tubules consisting of a mosaic of wild-type and Pax2/8 mutant proximal tubules cells were generated. Gene expression of mutant and wild-type proximal tubule cells was compared under homeostatic conditions using single-nucleus RNA sequencing. Overall design: Female mice heterozygous for the X-linked phosphoenolpyruvate carboxykinase Cre driver and conditional Pax2, Pax8, and tdTomato/green fluorescent protein reporter alleles were generated. The proximal tubules of these mice were composed of wild-type and Pax2/8 mutant cells due to random X-inactivation. 12-week-old uninjured mice were euthanized, and their kidneys were flash-frozen for single-nucleus RNA sequencing.