Selenom-KO Mouse

SELENOM, also known as selenoprotein M, is a selenoprotein located in the endoplasmic reticulum (ER) lumen. Selenoproteins, containing the 21st amino acid selenocysteine, play crucial roles in cellular homeostasis, often with oxidoreductase functions. SELENOM's thioredoxin motif suggests an oxidoreductase role, and it is involved in various biological processes like glucose metabolism and synaptic plasticity, and may impact redox signaling and energy metabolism [2,5].

Gene knockout studies have provided key insights into SELENOM's functions. In 10-month-old SELENOM knockout mice, there was a decrease in synaptic plasticity and memory impairment, along with hyperglycaemia and disturbed glucose metabolism. The knockout led to inhibition of the brain insulin signaling pathway (PI3K/AKT/mTOR/p70 S6 kinase pathway), which may be the cause of impaired synaptic plasticity. High-fat diet feeding in these knockout mice further suppressed the brain insulin signaling pathway and led to earlier cognitive impairment at 5 months of age [1]. In adipose tissue of SelenoM-deficient mice, there were glycolipid metabolic disturbances, insulin resistance, and aggravated meta-inflammation via the Hippo-YAP/TAZ-ROS signaling axis [4]. In the A-172 human glioblastoma cell line, knockdown of SELENOM led to ER stress, an increase in pro-apoptotic gene expression, but without inducing cell death likely due to compensatory increases in other antioxidant genes [3].

In summary, SELENOM plays vital roles in brain glucose metabolism, synaptic plasticity, and the regulation of apoptosis, ER stress, and calcium homeostasis. Gene knockout mouse models have revealed its significance in cognitive function and metabolic-related diseases, highlighting its potential as a therapeutic target for treating cognitive and metabolic disorders [1,3,4].

References:

1. Lin, Shujing, Chen, Chen, Ouyang, Pei, Zhang, Zhonghao, Song, Guo-Li. 2023. SELENOM Knockout Induces Synaptic Deficits and Cognitive Dysfunction by Influencing Brain Glucose Metabolism. In Journal of agricultural and food chemistry, 71, 1607-1619. doi:10.1021/acs.jafc.2c07491. https://pubmed.ncbi.nlm.nih.gov/36635091/

2. Nunes, Lance G A, Cain, Antavius, Comyns, Cody, Hoffmann, Peter R, Krahn, Natalie. 2023. Deciphering the Role of Selenoprotein M. In Antioxidants (Basel, Switzerland), 12, . doi:10.3390/antiox12111906. https://pubmed.ncbi.nlm.nih.gov/38001759/

3. Varlamova, Elena G, Goltyaev, Michael V, Turovsky, Egor A. 2022. The Role of Selenoproteins SELENOM and SELENOT in the Regulation of Apoptosis, ER Stress, and Calcium Homeostasis in the A-172 Human Glioblastoma Cell Line. In Biology, 11, . doi:10.3390/biology11060811. https://pubmed.ncbi.nlm.nih.gov/35741332/

4. Cai, Jingzeng, Huang, Jiaqiang, Li, Di, Xu, Shiwen, Zhang, Ziwei. 2024. Hippo-YAP/TAZ-ROS signaling axis regulates metaflammation induced by SelenoM deficiency in high-fat diet-derived obesity. In Journal of advanced research, 71, 603-620. doi:10.1016/j.jare.2024.06.005. https://pubmed.ncbi.nlm.nih.gov/38879122/

5. Gong, Ting, Hashimoto, Ann C, Sasuclark, Alexandru R, Gurary, Alexandra, Pitts, Matthew W. 2019. Selenoprotein M Promotes Hypothalamic Leptin Signaling and Thioredoxin Antioxidant Activity. In Antioxidants & redox signaling, 35, 775-787. doi:10.1089/ars.2018.7594. https://pubmed.ncbi.nlm.nih.gov/30648404/