huMMP7(2) Mouse
Product Name
huMMP7(2) Mouse
Product ID
C002038
Strain Name
C57BL/6JCya-Mmp7tm2(hMMP7)/Cya
Backgroud
C57BL/6JCya
Status
When using this mouse strain in a publication, please cite “huMMP7(2) Mouse (Catalog C002038) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
MMP7
Gene Alias
MMP-7, MPSL1, PUMP-1
NCBI ID
Chromosome
Chr 11 (Human)
MGI ID
Datasheet
Strain Description
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(2) mouse is a humanized model generated via gene editing. The sequence from the start codon to 3'UTR of the mouse Mmp7 was replaced with the sequence from the start codon to 3'UTR of the human MMP7. This model is suitable for research on various cancers, inflammatory and fibrotic diseases, and cardiovascular conditions, as well as for the screening of MMP7-targeted therapeutics and preclinical pharmacological evaluation. Furthermore, Cyagen also offers the huMMP7 mouse model (Catalog No.: C001914). The huMMP7 mouse was generated on a C57BL/6NCya background by replacing the sequences from upstream of exon 1 to downstream of exon 6 of the mouse Mmp7 gene with the sequences from upstream of exon 1 to downstream of exon 6 of the human MMP7 (including promoter).
Reference
Wozniak J, Floege J, Ostendorf T, Ludwig A. Key metalloproteinase-mediated pathways in the kidney. Nat Rev Nephrol. 2021 Aug;17(8):513-527.
Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol. 2001;17:463-516.
de Almeida LGN, Thode H, Eslambolchi Y, Chopra S, Young D, Gill S, Devel L, Dufour A. Matrix Metalloproteinases: From Molecular Mechanisms to Physiology, Pathophysiology, and Pharmacology. Pharmacol Rev. 2022 Jul;74(3):712-768.
Liao HY, Da CM, Liao B, Zhang HH. Roles of matrix metalloproteinase-7 (MMP-7) in cancer. Clin Biochem. 2021 Jun;92:9-18.
Craig VJ, Zhang L, Hagood JS, Owen CA. Matrix metalloproteinases as therapeutic targets for idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol. 2015 Nov;53(5):585-600.
Liu G, Philp AM, Corte T, Travis MA, Schilter H, Hansbro NG, Burns CJ, Eapen MS, Sohal SS, Burgess JK, Hansbro PM. Therapeutic targets in lung tissue remodelling and fibrosis. Pharmacol Ther. 2021 Sep;225:107839.
Cathcart J, Pulkoski-Gross A, Cao J. Targeting Matrix Metalloproteinases in Cancer: Bringing New Life to Old Ideas. Genes Dis. 2015 Mar 1;2(`1):26-34.
Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, Ramirez-Acuña JM, Perez-Romero BA, Guerrero-Rodriguez JF, Martinez-Avila N, Martinez-Fierro ML. The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. Int J Mol Sci. 2020 Dec 20;21(24):9739.
Strain Strategy
The sequence from the start codon to 3'UTR of the mouse Mmp7 was replaced with the sequence from
the start codon to 3'UTR of the human MMP7.
Figure 1. Gene editing strategy for huMMP7(2) mice.
Application Area
Development, screening, and preclinical pharmacodynamic evaluation of MMP7-targeted drugs;
Research on the occurrence and prognosis of cancers, such as colorectal, gastric, pancreatic, and lung cancers;
Studies on inflammatory diseases, like inflammatory bowel disease, chronic obstructive pulmonary disease, and asthma;
Research on fibrotic diseases, such as idiopathic pulmonary fibrosis;
Studies on cardiovascular diseases, such as atherosclerosis and aneurysms.
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