T-Cell Factor/β-Catenin Activity is Suppressed Normally in Two Independent Models of Autosomal Dominant Polycystic Kidney Disease

摘要

During murine kidney development, canonical WNT signalling is highly active in the renal tubules until about embryonic day E16-E18 when β-catenin transcriptional activity becomes progressively restricted to the nephrogenic zone. Several in vitro studies have found a link between cilial signalling and β-catenin regulation. The cilial protein genes PKD1 and PKD2 are known to be mutated in autosomal dominant polycystic kidney disease and previous studies proposed that these mutations could lead to a failure to suppress canonical WNT signalling activity; aberrant activity might then contribute to the cystic phenotype. However, in this study, we show that suppression of canonical WNT activity, defined by a TCF/β-catenin-lacZ reporter, is normal in two independent models of polycystic kidney disease. We crossed a TCF/β-catenin-lacZ reporter mouse with mice Pkd1 or Pkd2 mutations and found that there was no β-galactosidase staining in cells lining the renal cysts. This suggests that excessive β-catenin transcriptional activity may not contribute to cystogenesis in these models of autosomal dominant polycystic kidney disease.