PKHD1 and autosomal recessive polycystic kidney disease: These combinations demonstrated that (1) Prkcsh and Sec63 mutations result in impaired biogenesis of PC1; (2) PC1 dosage modifies the severity of both ADPKD and ARPKD; (3) the threshold level of PC1 necessary for normal tubular morphology varies by nephron segment with collecting ducts being most sensitive; and (4) overexpression of Pkd1 is capable of rescuing a mutant Pkhd1 animal (38).