Gas6-KO Mouse

Gas6, also known as growth arrest-specific gene 6, is a 75-kDa vitamin K-dependent protein belonging to the vitamin K-dependent family of proteins [1]. It binds to receptors Tyro3, Axl, and Mer (TAM) in the Gas6/TAM signaling pathway, regulating cell proliferation, survival, and migration, and is expressed in many human tissues [3]. This pathway is of great biological importance as it is involved in multiple physiological and pathological processes. Genetic models, such as gene knockout (KO) mouse models, are valuable for studying Gas6.

In sepsis, Gas6 knockout in mice removed the beneficial effects of its overexpression, which included improvement of cardiac dysfunction, alleviation of mitochondrial injury, endoplasmic reticulum stress, oxidative stress, and apoptosis. This indicates Gas6's role in protecting against sepsis-induced cardiac dysfunction through the NLRP3 inflammasome-dependent mechanism [1]. In myocardial ischemia-reperfusion (IR) injury, down-regulated levels of Gas6 were observed in murine hearts. Gas6 overexpression significantly improved cardiac function, while gain-and loss-of-function experiments determined its role in protecting against mitochondrial dysfunction, oxidative stress, and apoptosis, suggesting Gas6 as a potential target for myocardial IR injury management [2].

In conclusion, Gas6 plays essential roles in various biological processes, especially in protecting against diseases like sepsis-induced cardiac dysfunction and myocardial IR injury. Studies using KO mouse models have been crucial in revealing these functions, providing insights into potential therapeutic strategies for these disease areas.

References:

1. Ji, Ting, Liu, Qiong, Yu, Liming, Ren, Jun, Yang, Yang. 2023. GAS6 attenuates sepsis-induced cardiac dysfunction through NLRP3 inflammasome-dependent mechanism. In Free radical biology & medicine, 210, 195-211. doi:10.1016/j.freeradbiomed.2023.11.007. https://pubmed.ncbi.nlm.nih.gov/37979891/

2. Lu, Chenxi, Song, Yanbin, Wu, Xiaopeng, Ren, Jun, Yang, Yang. 2024. Pleiotropic role of GAS6 in cardioprotection against ischemia-reperfusion injury. In Journal of advanced research, 70, 481-497. doi:10.1016/j.jare.2024.04.020. https://pubmed.ncbi.nlm.nih.gov/38653371/

3. Wu, Guiling, Ma, Zhiqiang, Cheng, Yicheng, Chen, Fulin, Yang, Yang. 2018. Targeting Gas6/TAM in cancer cells and tumor microenvironment. In Molecular cancer, 17, 20. doi:10.1186/s12943-018-0769-1. https://pubmed.ncbi.nlm.nih.gov/29386018/