Kidney-specific deletion of the BicC family RNA binding protein 1 triggers an ADPKD-like cystogenic program

Cystic kidneys with elevated cAMP levels also develop in mouse embryos lacking the BicC family RNA-binding protein 1 (Bicc1). To prevent embryonic lethality, we flanked Bicc1 exon 4 with loxP sites for conditional knockout (cKO) in renal tubules using inducible Pax8rtTA-driven Cre in adults, or distal segment-specific deletion in utero using Ksp-Cre.

Whereas Bicc1-deficient adult kidneys formed relatively few cysts within six months, distal nephron-specific deletion induced aggressive PKD-like disease. Automated Renal Tubule Cyst Quantification (ARTCyQ), a novel machine-learning pipeline to analyze immunofluorescent stainings, revealed increasing ambiguity in nephron segment identity and activation of ADPKD-related pathways, including YAP signaling. Accordingly, transcriptional profiling revealed overlap with PKD and injury-repair signatures, supporting a role for Bicc1 in polycystin signaling.