huMST1(2) Mouse
製品名
huMST1(2) Mouse
製品ID
C002110
系統名
C57BL/6Cya-Mst1em1(hMST1)/Cya
背景情報
C57BL/6Cya
状況
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製品タイプ
年齢
遺伝子型
性別
数量
遺伝子名
遺伝子別名
MSP, HGFL, NF15S2, D3F15S2, DNF15S2
NCBI ID
染色体
Chr 3
MGI ID
さらに
系統詳細
MST1 (Macrophage stimulating 1), also known as hepatocyte growth factor-like protein (HGFL) or macrophage-stimulating protein (MSP), is a secreted growth factor belonging to the kringle protein family and is homologous to hepatocyte growth factor (HGF) [1–2]. It is predominantly expressed in the liver and regulates macrophage chemotaxis, phagocytosis, morphological changes, and the production of inflammatory mediators by binding to its receptor RON (MST1R). MST1 also plays a role in physiological processes such as ciliary motility [3–4]. The nonsynonymous coding variant rs3197999 (R689C) in the MST1 gene is significantly associated with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, as well as primary sclerosing cholangitis (PSC) [5–6].
The huMST1(2) mouse was generated using gene-editing technology to replace the endogenous mouse Mst1 gene sequence from the 5′ untranslated region (5′UTR) to the 3′ untranslated region (3′UTR) with the corresponding human MST1 gene sequence spanning the 5′UTR to the 3′UTR. This model is primarily applicable to mechanistic studies of inflammatory bowel disease (IBD), primary sclerosing cholangitis, macrophage-associated inflammation, and immune regulation, as well as the exploration of therapeutic strategies targeting the MST1/MSP–RON pathway. It can be used to evaluate the potential effects of related drugs in inflammatory and immune diseases.
参考文献
Yoshimura, T., Yuhki, N., Wang, M H., Skeel, A., & Leonard, E J.. (1993). Cloning, sequencing, and expression of human macrophage stimulating protein (MSP, MST1) confirms MSP as a member of the family of kringle proteins and locates the MSP gene on chromosome 3. The Journal of biological chemistry, 268(21), 15461-8.
Han, S., Stuart, L A., & Degen, S J.. (1991). Characterization of the DNF15S2 locus on human chromosome 3: identification of a gene coding for four kringle domains with homology to hepatocyte growth factor. Biochemistry, 30(40), 9768-80.
Skeel, A., Yoshimura, T., Showalter, S D., Tanaka, S., & Appella, E.. (1991). Macrophage stimulating protein: purification, partial amino acid sequence, and cellular activity. The Journal of experimental medicine, 173(5), 1227-34.
Sakamoto, O., Iwama, A., Amitani, R., Takehara, T., & Yamaguchi, N.. (1997). Role of macrophage-stimulating protein and its receptor, RON tyrosine kinase, in ciliary motility. The Journal of clinical investigation, 99(4), 701-9.
Goyette, P., Lefebvre, C., Ng, A., Brant, S R., & Cho, J H.. (2008). Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis. Mucosal immunology, 1(2), 131-8.
Melum, Espen., Franke, Andre., Schramm, Christoph., Weismüller, Tobias J., & Gotthardt, Daniel Nils.. (2010). Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci. Nature genetics, 43(1).
系統作製戦略
The sequence of the endogenous mouse Mst1 gene from the 5′UTR to the 3′UTR was replaced with that of the human MST1 gene from the 5′UTR to the 3′UTR. The KI region may affect the expression of mouse Mir7088, while its effect on mouse Rnf123 remains unclear.
Figure 1. Gene editing strategy of huMST1(2) mice.
適用分野
Mechanistic studies of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, primary sclerosing cholangitis (PSC), macrophage-associated inflammation, and immune regulation;
Exploration of therapeutic strategies targeting the MST1/MSP–RON pathway.
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