Mmp1a, the murine homologue of human Matrix Metalloproteinase 1 (MMP1), is a key enzyme involved in extracellular matrix (ECM) degradation and remodeling. It functions in various biological processes and is associated with multiple disease-related pathways, such as those in cancer, atherosclerosis, and intervertebral disc degeneration [1,2,4]. Genetic models, especially mouse models, are valuable for studying Mmp1a due to the lack of a well-characterized murine homologue of MMP1 previously [1].

In Mmp1a-deficient mice, studies have shown that Mmp1a deficiency suppresses tumor growth and angiogenesis in lung cancer models. Co-implantation of wild-type fibroblasts restored tumor growth, highlighting the role of stromal-derived Mmp1a. Silencing of PAR1 in lung carcinoma cells phenocopied Mmp1a-deficiency, validating PAR1 as a target [3]. Also, Mmp1a-knockout mice have decreased susceptibility to chemical carcinogen-induced lung carcinomas, with smaller tumors, and proteomic analysis suggested Mmp1a may modulate the Th1/Th2 inflammatory response [5]. In the context of atherosclerosis, Mmp1a deficiency suppresses its development in mice [2].

In conclusion, Mmp1a is crucial for tumorigenesis, angiogenesis, and the development of atherosclerosis as revealed through gene-knockout mouse models. These models have provided significant insights into Mmp1a's role in these disease areas, helping to understand its functions in the context of disease-related biological processes.

References:

1. Foley, Caitlin J, Kuliopulos, Athan. . Mouse matrix metalloprotease-1a (Mmp1a) gives new insight into MMP function. In Journal of cellular physiology, 229, 1875-80. doi:10.1002/jcp.24650. https://pubmed.ncbi.nlm.nih.gov/24737602/

2. Fletcher, Elizabeth K, Wang, Yanling, Flynn, Laura K, Covic, Lidija, Kuliopulos, Athan. 2021. Deficiency of MMP1a (Matrix Metalloprotease 1a) Collagenase Suppresses Development of Atherosclerosis in Mice: Translational Implications for Human Coronary Artery Disease. In Arteriosclerosis, thrombosis, and vascular biology, 41, e265-e279. doi:10.1161/ATVBAHA.120.315837. https://pubmed.ncbi.nlm.nih.gov/33761760/

3. Foley, C J, Fanjul-Fernández, M, Bohm, A, López-Otín, C, Kuliopulos, A. 2013. Matrix metalloprotease 1a deficiency suppresses tumor growth and angiogenesis. In Oncogene, 33, 2264-72. doi:10.1038/onc.2013.157. https://pubmed.ncbi.nlm.nih.gov/23708660/

4. Lei, Yu, Zhan, Enyu, Chen, Chao, Li, Xingguo, Zhang, Fan. 2024. ALKBH5-mediated m6A demethylation of Runx2 mRNA promotes extracellular matrix degradation and intervertebral disc degeneration. In Cell & bioscience, 14, 79. doi:10.1186/s13578-024-01264-y. https://pubmed.ncbi.nlm.nih.gov/38877576/

5. Fanjul-Fernández, Miriam, Folgueras, Alicia R, Fueyo, Antonio, Freije, José M P, López-Otín, Carlos. 2013. Matrix metalloproteinase Mmp-1a is dispensable for normal growth and fertility in mice and promotes lung cancer progression by modulating inflammatory responses. In The Journal of biological chemistry, 288, 14647-14656. doi:10.1074/jbc.M112.439893. https://pubmed.ncbi.nlm.nih.gov/23548910/