Ccr1-flox Mouse

Ccr1, the CC chemokine receptor 1, is a G protein-linked receptor predominantly expressed in various leukocytes. It binds to CC chemokines like CCL5 (RANTES) and CCL3 (MIP-1alpha), and is involved in regulating inflammatory responses. Ccr1 is essential for monocyte extravasation and transportation during inflammation, and is considered a promising target for anti-inflammatory therapy [1,2].

In multiple myeloma, CCL3 and CCR1 play a central role in the pathogenesis and MM-induced osteolytic bone disease. CCR1 stimulation leads to tumor growth via upregulation of cell adhesion and cytokine secretion, and also modulates the osteoclast/osteoblast balance. Targeting CCR1 with antagonists in murine and humanized mouse models can control tumor burden and prevent osteolysis [3].

In non-alcoholic steatohepatitis (NASH), CCR1 is upregulated. Ccr1-deficient mice (systemic Ccr1-/-and liver macrophage-knockout Ccr1LKD) fed a high-cholesterol and high-fat or methionine/choline-deficient diet showed inhibited NASH-associated hepatic steatosis, inflammation, and fibrosis. CCR1 inhibitor BX471 also effectively suppressed NASH progression in mice, suggesting CCR1 regulates macrophage activation through mTORC1 signaling in NASH [4].

In conclusion, Ccr1 is crucial in inflammatory processes. Its role in multiple myeloma and NASH has been revealed through gene-knockout mouse models. These findings indicate that targeting Ccr1 could be a potential therapeutic approach for these diseases.