Ltb4r2-flox Mouse

Ltb4r2, also known as BLT2, is a low-affinity receptor for several key eicosanoids and chemoattractants. It is involved in multiple biological processes related to inflammation and cancer. Leukotrienes, the ligands of Ltb4r2, are arachidonic acid-derived bioactive molecules known as mediators of allergic and inflammatory reactions [2].

In liver tumorigenesis, selective ablation of Scd2 in activated hepatic stellate cells (aHSC) globally suppresses nuclear CTNNB1 and YAP1 in tumors and the tumor microenvironment, and prevents liver tumorigenesis in male mice. This is associated with reduced Ltb4r2 and its ligand 12-HHTrE. Genetic or pharmacological inhibition of Ltb4r2 recapitulates CTNNB1 and YAP1 inactivation and tumor suppression in culture and in vivo, suggesting that the 12-HHTrE-Ltb4r2-CTNNB1-YAP1 pathway initiated by aHSC is a potential HCC therapeutic target [1].

In the context of tissue inflammation, studies using Ltb4r2-/-mice and zebrafish models with blt2a knockdown or chemical inhibition of BLT2 signaling show that Ltb4r2 is required for macrophage chemotactic function during inflammation, implicating it as a potential therapeutic target for inflammatory pathologies [3].

In conclusion, Ltb4r2 plays crucial roles in inflammation-related macrophage migration and in promoting liver tumorigenesis through the activation of specific signaling cascades. The use of gene-knockout mouse models and other loss-of-function experiments in these studies has revealed its significance in these biological processes and disease conditions, highlighting its potential as a therapeutic target for liver cancer and inflammatory pathologies.