huMST1(2) Mouse

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.