Rasd1-KO Mouse

Rasd1, also known as Dexamethasone-induced Ras-related protein 1 (Dexras1) or AGS1, is a member of the Ras superfamily of monomeric G proteins. It has a regulatory function in signal transduction and is involved in various biological processes such as iron homeostasis, growth hormone secretion, and circadian rhythm [3,4]. It may also participate in intracellular signaling pathways related to neurons [2].

In subarachnoid hemorrhage (SAH), Rasd1 knockdown improved neurobehavior, glia polarization, oxidative stress, neuroinflammation, ferroptosis, and demyelination, while its overexpression aggravated these changes. Mechanistically, Rasd1 can induce oligodendrocyte ferroptosis through inhibiting UCP2, increasing ROS, and activating NCOA4-mediated ferritinophagy, suggesting it plays a role in white matter injury after SAH [1]. In oocytes, Rasd1 knockdown arrested GV oocytes at the MI stage, disrupted meiotic spindling and chromosomal alignment, indicating its role in MI-MII oocyte transition [3]. In metabolic dysfunction-associated steatotic liver disease (MASLD), RASD1 knockdown reduced lipid deposition in hepatocytes and mice, regulating lipid metabolism through the PI3K/AKT/mTOR signaling pathway [5].

In summary, Rasd1 is crucial in multiple biological processes. Studies using knockdown models have revealed its roles in white matter injury after SAH, oocyte maturation, and MASLD progression. These findings contribute to understanding the pathogenesis of related diseases and may provide potential therapeutic targets.

References:

1. Fu, Wenqiao, Che, Xudong, Tan, Jiahe, Wen, Tangmin, He, Zhaohui. 2023. Rasd1 is involved in white matter injury through neuron-oligodendrocyte communication after subarachnoid hemorrhage. In CNS neuroscience & therapeutics, 30, e14452. doi:10.1111/cns.14452. https://pubmed.ncbi.nlm.nih.gov/37735980/

2. Durmaz, Ceren Damla, Karabulut, Halil Gürhan, Saka, Meram Can, Atbaşoğlu, Cem, Ilgın Ruhi, Hatice. 2022. Genetic Analysis of RASD1 as a Candidate Gene for Schizophrenia. In Balkan medical journal, 39, 422-428. doi:10.4274/balkanmedj.galenos.2022.2022-5-90. https://pubmed.ncbi.nlm.nih.gov/36305088/

3. Lee, Youngeun, Kim, Kyeoung-Hwa, Yoon, Hyemin, Chang, Eun Mi, Choi, Youngsok. 2016. RASD1 Knockdown Results in Failure of Oocyte Maturation. In Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 40, 1289-1302. doi:10.1159/000453182. https://pubmed.ncbi.nlm.nih.gov/27997888/

4. Foradori, Chad D, Mackay, Laci, Huang, Chen-Che J, Kemppainen, Robert J. 2021. Expression of Rasd1 in mouse endocrine pituitary cells and its response to dexamethasone. In Stress (Amsterdam, Netherlands), 24, 659-666. doi:10.1080/10253890.2021.1907340. https://pubmed.ncbi.nlm.nih.gov/33840368/

5. Zeng, Guifang, Liu, Xialei, Zheng, Zhouying, Zou, Baojia, Li, Jian. 2024. Knockdown of RASD1 improves MASLD progression by inhibiting the PI3K/AKT/mTOR pathway. In Lipids in health and disease, 23, 424. doi:10.1186/s12944-024-02419-z. https://pubmed.ncbi.nlm.nih.gov/39731125/