Rapamycin-mediated suppression of renal cyst expansion in del34 Pkd1-/- mutant mouse embryos: an investigation of the feasibility of renal cyst prevention in the foetus.

摘要: : Aim:  Polycystic kidney disease (PKD) in humans involves cyst expansion beginning utero. Recessive PKD can result end-stage renal (ESRD) within the first decade, whereas autosomal dominant (ADPKD), caused by mutations PKD1 or PKD2 gene, typically leads to ESRD fifth decade of life. Inhibition mTOR signalling was recently found halt formation adult ADPKD mice. In contrast, no studies have investigated potential treatments prevent utero recessive PKD. Given that homozygous Pkd1 mutant mice exhibit utero, we decided investigate whether inhibition ameliorates foetal mice. Methods:  Pregnant Pkd1+/− female (mated with male mice) were treated rapamycin from E14.5 E17.5. Foetal kidneys dissected, genotyped and evaluated size as well expression developmental marker, Pax2. Results:  Numerous cysts present Pkd1−/− kidneys, which twice weight wild-type kidneys. Cyst reduced a third rapamycin-treated sections mass near levels. However, total number not compared control embryos. Pax2 development unaltered but some lethality observed null embryos. Conclusion:  Rapamycin treatment reduces mice; therefore, prevention is feasible. selective rapamycin-associated limits its usefulness