Ccr1-KO Mouse

Ccr1, the CC chemokine receptor 1, is a G protein-coupled receptor predominantly expressed in various leukocytes. It binds to CC chemokines like CCL5 (RANTES) and CCL3 (MIP-1α), and is crucial in regulating inflammatory responses, monocyte extravasation, and transportation in inflammatory conditions [2,3]. It is involved in the "chemokine network", which is vital for both normal bone microenvironment and the tumor microenvironment of multiple myeloma [1].

In multiple myeloma models, in vivo studies of Ccr1 antagonists have shown they can reduce tumor burden, minimize osteolytic bone damage, deter metastasis, and limit disease progression, suggesting Ccr1 plays a role in the pathogenesis of multiple myeloma [1]. In non-alcoholic steatohepatitis (NASH) mouse models, Ccr1-deficient mice (Ccr1-/-) fed a high-cholesterol and high-fat or methionine/choline-deficient diet showed inhibition of NASH-associated hepatic steatosis, inflammation, and fibrosis. This indicates Ccr1 promotes NASH progression, likely through regulating macrophage activation via mTORC1 signaling [4].

In conclusion, Ccr1 is essential in regulating inflammatory responses and monocyte movement. Model-based research, especially using Ccr1-deficient mouse models, has revealed its significance in diseases like multiple myeloma and NASH. Understanding Ccr1's functions provides potential therapeutic targets for these diseases.

References:

1. Gilchrist, Annette, Echeverria, Stephanie L. 2022. Targeting Chemokine Receptor CCR1 as a Potential Therapeutic Approach for Multiple Myeloma. In Frontiers in endocrinology, 13, 846310. doi:10.3389/fendo.2022.846310. https://pubmed.ncbi.nlm.nih.gov/35399952/

2. Tian, Qi, Yan, Ziang, Guo, Yujia, Chen, Zhibiao, Li, Mingchang. 2024. Inflammatory Role of CCR1 in the Central Nervous System. In Neuroimmunomodulation, 31, 173-182. doi:10.1159/000540460. https://pubmed.ncbi.nlm.nih.gov/39116843/

3. Saeki, Toshihiko, Naya, Akira. . CCR1 chemokine receptor antagonist. In Current pharmaceutical design, 9, 1201-8. doi:. https://pubmed.ncbi.nlm.nih.gov/12769747/

4. Li, Haoran, Pan, Tongtong, Gao, Lingjia, Ding, Chunming, Xu, Liang. 2023. Chemokine receptor CCR1 regulates macrophage activation through mTORC1 signaling in nonalcoholic steatohepatitis. In Metabolism: clinical and experimental, 151, 155758. doi:10.1016/j.metabol.2023.155758. https://pubmed.ncbi.nlm.nih.gov/38070823/