Corin-KO Mouse

Corin is a type II transmembrane serine protease highly expressed in the heart. Its essential function is to convert the atrial natriuretic peptide (ANP) precursor to mature ANP, a crucial element in cardiac endocrine function that promotes natriuresis, diuresis, and vasodilation, thus maintaining normal blood pressure and cardiac function. It may also be involved in the PI3K/AKT and NF-κB pathways, as suggested by in-vitro studies on cardiomyocytes [1].

In mice, lack of corin (a form of gene knockout) prevents ANP activation. This leads to salt-sensitive hypertension, indicating the role of corin in maintaining normal blood pressure in vivo [2]. The hypertensive phenotype is exacerbated during pregnancy in these knockout mice. In addition, in two siblings with a homozygous null variant in CORIN, they presented with left atrial cardiomyopathy, hypertension, arrhythmia, and fibrosis, suggesting that corin is critical to normal ANP activity, left atrial function, and cardiovascular homeostasis [3].

In conclusion, Corin is key in the activation of ANP, which is vital for maintaining sodium homeostasis, blood pressure, and cardiac function. Gene knockout mouse models have been instrumental in revealing its role in hypertension, heart-related diseases, and pregnancy-induced hypertension, providing insights into the underlying mechanisms and potential therapeutic targets for these disease areas.

References:

1. Li, Yansong, Xia, Jingwen, Jiang, Nianxin, Wei, Yong, Zhang, Xuan. 2017. Corin protects H2O2-induced apoptosis through PI3K/AKT and NF-κB pathway in cardiomyocytes. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 97, 594-599. doi:10.1016/j.biopha.2017.10.090. https://pubmed.ncbi.nlm.nih.gov/29101802/

2. Wu, Qingyu, Xu-Cai, Ye Olivia, Chen, Shenghan, Wang, Wei. 2008. Corin: new insights into the natriuretic peptide system. In Kidney international, 75, 142-6. doi:10.1038/ki.2008.418. https://pubmed.ncbi.nlm.nih.gov/18716601/

3. Baris Feldman, Hagit, Chai Gadot, Chofit, Zahler, David, Kurolap, Alina, Ablin, Jacob N. . Corin and Left Atrial Cardiomyopathy, Hypertension, Arrhythmia, and Fibrosis. In The New England journal of medicine, 389, 1685-1692. doi:10.1056/NEJMoa2301908. https://pubmed.ncbi.nlm.nih.gov/37913506/