Pdzk1-flox Mouse

PDZK1, belonging to the Na+/H+ Exchanger (NHE) regulatory factor family, is a PDZ protein. It plays crucial roles in multiple biological processes and disease-related pathways. PDZK1 has been shown to be involved in pathways such as those related to mitochondrial function, epidermal growth factor receptor (EGFR) signaling, and platelet-derived growth factor receptor-β (PDGFR-β) signaling, with implications for diseases like osteoarthritis (OA), triple-negative breast cancer (TNBC), and clear cell renal cell carcinoma (ccRCC) [1,2,3].

In OA, Pdzk1 knockout in chondrocytes exacerbates mechanical overload-induced cartilage degeneration, indicating its protective role against mechanical overload-induced chondrocyte senescence and OA by targeting mitochondrial function [1].

In TNBC, PDZK1 downregulation is related to erlotinib resistance. PDZK1 binds to EGFR, promoting its degradation and inhibiting phosphorylation, and its restoration can reverse the degree of cell malignancy [2].

In ccRCC, PDZK1 is significantly downregulated in sunitinib-resistant specimens, and it negatively regulates PDGFR-β phosphorylation and downstream pathways, with miR-15b antagomirs enhancing sunitinib cytotoxicity by upregulating PDZK1 [3].

In conclusion, PDZK1 is essential in various biological functions and disease-related pathways. Gene knockout studies in mouse models, such as in OA, TNBC, and ccRCC, have revealed its key roles in disease development and response to treatment. These findings highlight PDZK1 as a potential therapeutic target for these diseases.