The Human CD2 promoter-Kozak-iCre-Human CD2 3'UTR-Human CD2 LCR cassette was inserted into the H11 locus. Cre recombinase is expressed under the regulatory control of the human CD2 promoter.

MMP7 encodes matrix metalloproteinase-7 (MMP-7), also known as matrilysin, a member of the matrix metalloproteinase family that plays a crucial role in the degradation and remodeling of extracellular matrix (ECM) components ^[1]. MMP7 is primarily expressed in epithelial tissues of the gastrointestinal tract, lungs, and reproductive system. Cytokines, growth factors, hypoxia, and inflammatory signals regulate its expression. MMP7 is secreted as a zymogen and activated by other proteases or autolytic cleavage. Activated MMP7 can degrade ECM components such as collagen, proteoglycans, elastin, and fibronectin, and can also activate antimicrobial peptides (e.g., defensins) and process cytokines ^[2]. Functionally, MMP7 involves various physiological and pathological processes, including ECM remodeling, immune regulation, wound healing, and tumor progression. It is notably significant in tumor invasion and metastasis, where it promotes cancer cell migration by degrading matrix barriers and accelerates tumor growth by regulating angiogenesis and immune evasion ^[2-3]. MMP7 is associated with several diseases, including cancers (e.g., colorectal, gastric, pancreatic, and lung cancers, with high expression often correlated with poor prognosis), inflammatory diseases (e.g., inflammatory bowel disease, chronic obstructive pulmonary disease, and asthma), fibrotic diseases (e.g., idiopathic pulmonary fibrosis), and cardiovascular diseases (e.g., atherosclerosis and aneurysms) ^[3-5]. Hence, MMP7 is an important therapeutic target for various diseases. However, clinical trials targeting MMP7 face challenges in efficacy and safety. Broad-spectrum MMP inhibitors (e.g., Marimastat and Batimastat) have limited efficacy due to low specificity and adverse effects like musculoskeletal pain. Recent research focuses on selective MMP7-targeted inhibitory therapies, including small molecule inhibitors, monoclonal antibodies, peptide inhibitors, small interfering RNA (siRNA), and antisense oligonucleotides (ASO) ^[5-8]. MMP7 plays dual roles in maintaining physiological homeostasis and mediating pathological processes (particularly in cancer and fibrosis), making it a promising yet challenging therapeutic target. The huMMP7 mouse is a humanized model constructed by gene-editing technology. The sequences from upstream of exon 1 to downstream of exon 6 of the mouse Mmp7 gene were replaced with the sequences from upstream of exon 1 to downstream of exon 6 of the human MMP7 (including promoter). This model can be used for the research of various cancers, inflammatory diseases, fibrotic diseases, and cardiovascular diseases, as well as for the development of MMP7-targeted drugs.

Nudt19 is located on chromosome 7 of mice. SgRNA and ssDNA will be designed using Nuclease Technology; Nudt19 conditional knockout mice will be obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm will be collected for cryopreservation.

Adam5 is located on chromosome 8 of mice. Nuclease Technology will be used to design sgRNA; Adam5 knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.