Dkk1-flox Mouse

Dickkopf-1 (Dkk1) is a well-characterized Wnt inhibitor and a component of the Wnt/β -catenin signaling pathway. The Wnt signaling pathway is fundamental in cell fate determination, cell proliferation, and survival, and Dkk1's dysregulation is linked to multiple abnormal pathologies [3].

In gastric cancer, Dkk1 promotes tumor immune evasion. In vitro coculture assays showed it induces macrophages to become immunosuppressive, inhibiting antitumor responses of CD8+ T cells and NK cells. In vivo DKK1 blockade in syngeneic gastric cancer mouse models reprogramed tumor-associated macrophages (TAMs), restored immune activity in the tumor immune microenvironment, and triggered tumor regression. This also augmented the efficacy of programmed cell death protein-1 (PD-1) blockade [1].

In endometrial fibrosis, DKK1 loss promoted the fibrotic phenotype in DKK1 conditional knockout (CKO) mice. In vitro, DKK1 knockout suppressed the autophagic flux of endometrial stromal cells. DKK1 KO also promoted the secretion of interleukin (IL)-8 in exosomes, promoting macrophage proliferation and metastasis [2].

In conclusion, Dkk1 is a key regulator in the Wnt/β-catenin signaling pathway. Its dysregulation is associated with various diseases. The use of Dkk1 gene knockout and conditional knockout mouse models has revealed its role in tumor immune evasion in gastric cancer and endometrial fibrosis, providing potential therapeutic targets for these diseases.