Cma1-KO Mouse

Cma1, also known as Mcpt5 in mice, encodes chymase, a proteolytic enzyme. Chymase is mainly expressed in mast cells and is involved in various biological processes, such as tissue remodeling, fibrosis, and immune responses [1,2,6]. It may also play a role in the renin-angiotensin system, although the exact details are not fully elaborated in the given references [5].

A knock-in mouse model, Mcpt5/Cma1DTR, was generated where the human diphtheria toxin A receptor was expressed under the endogenous promoter of Mcpt5. Intraperitoneal injection of DT induced almost complete depletion of mast cells in heterozygote Mcpt5/Cma1DTR/+ mice, allowing for in-vivo study of mast cell-related functions associated with Cma1 [2]. In gastric cancer, high Cma1 expression was related to poor overall survival and progression-free survival, and was positively associated with the levels of infiltrated CD4+, CD8+ T cells, neutrophils, macrophages, and dendritic cells [1]. In psoriasis, Cma1 was among the differential genes identified that affected amino acid and carnitine metabolism, contributing to Th17 cell infiltration in psoriatic lesions [3]. In a Mexican population study, polymorphic repeats in Cma1 were associated with preeclampsia in women [4]. A genetic score from two predicted loss-of-function mutations in Cma1 showed no association with heart failure, chronic kidney disease or other predefined conditions [6]. In colorectal cancer, there was a shift in mast cell phenotype from Cma1high resting cells to activated cells [7]. In early pregnancy, MCs/rhuCMA1 promoted spiral-artery remodeling, which may be relevant to understanding pregnancy complications [8]. In eosinophilic esophagitis, a Cma1highCTSGhigh mast cell population remained activated even in disease remission [9]. In human lung mast cells, Cma1 was only detectable in a small proportion of cells [10].

In conclusion, Cma1 is a gene with diverse functions mainly through its role in mast cells. The Mcpt5/Cma1DTR mouse model and other genetic-based studies have been crucial in revealing its functions in diseases such as gastric cancer, psoriasis, preeclampsia, and in biological processes related to pregnancy, esophageal inflammation, and lung mast cell characteristics. Understanding Cma1 provides insights into disease mechanisms and potential therapeutic targets.

References:

1. Shi, Shanping, Ye, Shazhou, Mao, Jianmei, Tang, Xiaoli, Xi, Yang. 2020. CMA1 is potent prognostic marker and associates with immune infiltration in gastric cancer. In Autoimmunity, 53, 210-217. doi:10.1080/08916934.2020.1735371. https://pubmed.ncbi.nlm.nih.gov/32129682/

2. Sasaki, Hayato, Imanishi, Madoka, Fujikura, Daisuke, Okamura, Tadashi, Sasaki, Nobuya. 2021. New inducible mast cell-deficient mouse model (Mcpt5/Cma1DTR). In Biochemical and biophysical research communications, 551, 127-132. doi:10.1016/j.bbrc.2021.03.025. https://pubmed.ncbi.nlm.nih.gov/33725574/

3. Hu, XueQing, Qi, Cong, Feng, Fang, Li, Ping, Zhao, Jingxia. 2022. Combining network pharmacology, RNA-seq, and metabolomics strategies to reveal the mechanism of Cimicifugae Rhizoma - Smilax glabra Roxb herb pair for the treatment of psoriasis. In Phytomedicine : international journal of phytotherapy and phytopharmacology, 105, 154384. doi:10.1016/j.phymed.2022.154384. https://pubmed.ncbi.nlm.nih.gov/35963195/

4. Barragán-Zúñiga, L J, Sosa-Macias, M, Simental-Mendía, L E, Beltrán-Ontiveros, S, Galaviz-Hernandez, C. 2025. Association of (TG)n(GA)m repeats downstream CMA1 gene with preeclampsia in Mexican population. In Placenta, , . doi:10.1016/j.placenta.2025.03.018. https://pubmed.ncbi.nlm.nih.gov/40199686/

5. Soler, María José, Batlle, Daniel. 2021. Revisiting the renin-angiotensin system. In Molecular and cellular endocrinology, 529, 111268. doi:10.1016/j.mce.2021.111268. https://pubmed.ncbi.nlm.nih.gov/33819521/

6. Fairhurst-Hunter, Zammy, Walters, Robin G, Zink, Alexander, Chen, Zhengming, Millwood, Iona Y. 2022. Investigation into the Health Effects of Reduced Chymase Function Using Predicted Loss-of-Function Mutations in CMA1. In Journal of cardiovascular translational research, 15, 1474-1476. doi:10.1007/s12265-022-10261-w. https://pubmed.ncbi.nlm.nih.gov/35513594/

7. Xie, Zhenyu, Niu, Liaoran, Zheng, Gaozan, Zhang, Jian, Zheng, Jianyong. 2023. Single-cell analysis unveils activation of mast cells in colorectal cancer microenvironment. In Cell & bioscience, 13, 217. doi:10.1186/s13578-023-01144-x. https://pubmed.ncbi.nlm.nih.gov/38031173/

8. Zhang, Ningjuan, Schumacher, Anne, Fink, Beate, Zenclussen, Ana Claudia, Meyer, Nicole. 2022. Insights into Early-Pregnancy Mechanisms: Mast Cells and Chymase CMA1 Shape the Phenotype and Modulate the Functionality of Human Trophoblast Cells, Vascular Smooth-Muscle Cells and Endothelial Cells. In Cells, 11, . doi:10.3390/cells11071158. https://pubmed.ncbi.nlm.nih.gov/35406722/

9. Ben-Baruch Morgenstern, Netali, Ballaban, Adina Y, Wen, Ting, Barrett, Nora A, Rothenberg, Marc E. 2022. Single-cell RNA sequencing of mast cells in eosinophilic esophagitis reveals heterogeneity, local proliferation, and activation that persists in remission. In The Journal of allergy and clinical immunology, 149, 2062-2077. doi:10.1016/j.jaci.2022.02.025. https://pubmed.ncbi.nlm.nih.gov/35304158/

10. Rönnberg, Elin, Ravindran, Avinash, Mazzurana, Luca, Mjösberg, Jenny, Nilsson, Gunnar. 2023. Analysis of human lung mast cells by single cell RNA sequencing. In Frontiers in immunology, 14, 1151754. doi:10.3389/fimmu.2023.1151754. https://pubmed.ncbi.nlm.nih.gov/37063885/