Mylk-KO Mouse

MYLK, also known as myosin light chain kinase, catalyzes the phosphorylation of myosin light chains (MLC). It is involved in regulating smooth muscle contraction and cytoskeleton organization, thus playing a crucial role in various physiological processes. The gene is associated with signaling pathways like the transforming growth factor-β signaling pathway [1,3]. Genetic models, such as KO/CKO mouse models, are valuable for studying its functions.

In mice, aging-related aortic aneurysm and dissection (AAD) are aggravated via the miR-1204-MYLK signaling axis. miR-1204, which increases with age, directly targets MYLK, leading to vascular smooth muscle cell (VSMC) senescence, acquisition of a senescence-associated secretory phenotype (SASP), and loss of the contractile phenotype. MYLK overexpression can reverse these miR-1204-induced changes [1]. In humans, null variants in MYLK can result in heritable thoracic aortic disease. Missense pathogenic variant carriers experience earlier-onset aortic events compared to null pathogenic variant carriers [2].

In conclusion, MYLK is essential for smooth muscle function and cytoskeleton regulation. Mouse models have revealed its role in age-related aortic diseases. Understanding MYLK's functions provides insights into the mechanisms of aortic diseases and may offer potential therapeutic targets for these conditions.

References:

1. Liu, Ze-Long, Li, Yan, Lin, Yi-Jun, Ou, Zhi-Jun, Ou, Jing-Song. 2024. Aging aggravates aortic aneurysm and dissection via miR-1204-MYLK signaling axis in mice. In Nature communications, 15, 5985. doi:10.1038/s41467-024-50036-2. https://pubmed.ncbi.nlm.nih.gov/39013850/

2. Wallace, Stephanie E, Regalado, Ellen S, Gong, Limin, Colombo, Roberto, Milewicz, Dianna M. 2018. MYLK pathogenic variants aortic disease presentation, pregnancy risk, and characterization of pathogenic missense variants. In Genetics in medicine : official journal of the American College of Medical Genetics, 21, 144-151. doi:10.1038/s41436-018-0038-0. https://pubmed.ncbi.nlm.nih.gov/29925964/

3. Lin, Jie, He, Yihui, Chen, Lingfeng, Zang, Shengbing, Lin, Wansong. 2018. MYLK promotes hepatocellular carcinoma progression through regulating cytoskeleton to enhance epithelial-mesenchymal transition. In Clinical and experimental medicine, 18, 523-533. doi:10.1007/s10238-018-0509-2. https://pubmed.ncbi.nlm.nih.gov/29855744/