A novel ARPKD mouse model with near-complete deletion of the Polycystic Kidney and Hepatic Disease 1 (Pkhd1) genomic locus presents with multiple phenotypes but not renal cysts

Autosomal recessive polycystic kidney disease (ARPKD) is a pediatric hereditary disease with an incidence varying from 1 per 10,000 to 1 per 40,000 live births. Most cases result from mutations in polycystic kidney and hepatic disease 1 (PKHD1), a large gene that spans ∼469 kb1,2 and that undergoes complex splicing. Its longest open reading frame is encoded within a 67-exon mRNA transcript of ∼13 kb, which is translated into fibrocystin, a ciliary protein of 4074 amino acids. Although the variable severity of ARPKD is not completely understood,3 it has been observed that patients with truncating mutations in both alleles often die in the neonatal period, suggesting that in less severely affected patients partially functioning fibrocystin could offer some protection.