Pkd1-KO Mouse

Pkd1, encoding Polycystin-1, is one of the key genes related to autosomal dominant polycystic kidney disease (ADPKD), one of the most common monogenetic disorders. Mutations in Pkd1 and Pkd2 account for most ADPKD cases. Pkd1 contains a voltage-gated ion channel (VGIC) fold, which interacts with Pkd2 to form a non-canonical transient receptor potential (TRP) channel architecture [1].

PKD1 loss-of-function studies have shown diverse impacts. In murine models, Pkd1 re-expression from hybrid therapeutic constructs can ameliorate or eliminate polycystic kidney disease (PKD), indicating that Pkd1 intragenic sequences regulate expression levels and spatiotemporal patterns [3]. Pkd1 haploinsufficiency accelerated liver regeneration after partial hepatectomy, and Pkd1 loss protected against fatty liver disease, steatosis, and glucose intolerance, selectively increasing mTOR signaling without SREBP-1c activation [2]. In a porcine ADPKD model, PKD1 deficiency induced bronchiectasis by suppressing E-cadherin expression in the airway epithelial barrier, altering extracellular matrix components, and causing airway remodeling [4]. Also, in mice, Pkd1 interacts with Wnt5a in the non-canonical WNT signaling pathway to control lymphatic vascular morphogenesis, with loss of either gene suppressing the phenotypes seen in the other's knockout [5].

In conclusion, Pkd1 is crucial in multiple biological processes. Through gene-targeted strategies in animal models, its role in ADPKD, liver diseases, bronchiectasis, and lymphatic vascular development has been revealed. These findings provide insights into disease mechanisms and potential therapeutic targets related to Pkd1-associated pathologies.