Delayed cystogenesis and increased ciliogenesis associated with the re-expression of polaris in Tg737 mutant mice

Background. Renal cysts and shortened cilia on renal tubular epithelia have been observed in Tg737(orpk) (orpk ) mutant mice, suggesting a potential connection between cystogenesis and ciliogenesis. To further test this hypothesis we have characterized the progression of cystic disease and cilia expression in orpk , orpk ;Tg737Rsq (orpk rescue), and Tg737(Delta2-3betaGal) ;Tg737Rsq (KO rescue) mice. Methods. Orpk , orpk rescue, and KO rescue animals were generated and analyzed from postnatal day (P) 0 to P21 (orpk mutants) or from P0 to P210 (orpk rescue and KO rescue animals). Proximal tubules (PT) and collecting tubules (CT) were identified by immunohistochemistry using segment-specific lectins and a segment-specific cystic index was calculated. Scanning electron microscopy was utilized to observe and measure cilia expression in cysts from orpk , orpk rescue, and KO rescue animals. Results. KO rescue and orpk rescue animals develop adult-onset autosomal-recessive polycystic kidney disease (ARPKD). Ultrastructural analysis of cilia expression revealed that cysts from orpk expressed short cilia, whereas cysts from KO rescue animals expressed normal length cilia and cysts from orpk rescue animals expressed cilia that are two to five times longer than wild type. Conclusion. While this data is consistent with a role for polaris in ciliogenesis, it does not support a direct connection between ciliogenesis and cystic disease. Similarities in cyst formation and striking differences in cilia expression associated with these ARPKD mouse models indicates that cyst formation and cilia expression are independent phenotypic features regulated by polaris.