MST1 (Macrophage Stimulating 1), also known as hepatocyte growth factor-like protein (HGFL), is the natural ligand for the RON receptor tyrosine kinase. MST1 serves as a critical node connecting immune regulation and metabolic homeostasis. In tumor immunology, it shapes the immune landscape of the tumor microenvironment by regulating Treg stability, dendritic cell (DC) antigen presentation, macrophage polarization, and fundamental lymphocyte functions ^[1-2]. In metabolic diseases, it participates in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD), diabetes, and related complications through regulation of AMPK/SREBP-1c-mediated lipid metabolism signaling, mitophagy, and YAP signaling pathways ^[3-5]. The huMST1 mouse model is a humanized model generated using gene-editing technology, in which the mouse Mst1 genomic region was replaced with the corresponding human MST1 genomic sequence while retaining the murine signal peptide sequence. In tumor immunology, this model can be used to evaluate the regulatory effects of MST1 on the functions of CD8⁺ T cells and Treg cells, and to investigate MST1-mediated immune regulatory mechanisms and its interactions with the tumor microenvironment. In metabolic diseases, this model can be utilized to explore the pathogenic mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD), liver fibrosis, and diabetes, as well as the development of MST1-targeted therapeutics.

Sprr2k is located on chromosome 3 of mice. Nuclease Technology will be used to design sgRNA; Sprr2k knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

Psma3 is located on chromosome 12 of mice. SgRNA and ssDNA will be designed using Nuclease Technology; Psma3 conditional knockout mice will be obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm will be collected for cryopreservation.