Sgms1-KO Mouse

Sgms1, encoding sphingomyelin synthase 1, is an enzyme in the sphingosine-1-phosphate signalling pathway. It is involved in synthesizing sphingomyelin and diacylglycerol from phosphatidylcholine and ceramide, regulating intracellular vesicular transport, cholesterol metabolism, cell proliferation, apoptosis, etc [4].

In mice, the Sgms1tm1b allele, with exon 7 knockout and complete lack of detectable Sgms1 transcript in the inner ear, leads to progressive hearing loss starting from normal auditory thresholds, accompanied by a reduced endocochlear potential and abnormal stria vascularis [3]. In bone-related studies, SGMS1 addition accelerates MSC osteogenic differentiation, while SGMS1 silencing suppresses it. SGMS1 overexpression inhibits ceramide and promotes sphingomyelin levels, enhancing phosphorylated Akt, Runx2, and VEGF levels through regulating Cer/SM metabolism, and promoting rat bone regeneration in vivo [1]. In liver development, Sgms1 overexpression can ameliorate the abnormality of Mettl3-deficient liver caused by sphingolipid metabolism rewiring due to decreased decay of Smpd3 transcripts [2]. Also, SGMS1 knockout reduces sphingomyelin levels, inhibiting the replication of RNA viruses like SFTSV, SARS-CoV-2, and LCMV [5].

In summary, Sgms1 plays crucial roles in multiple biological processes. Gene-knockout mouse models have revealed its significance in hearing, bone formation, liver development, and RNA virus replication. Understanding Sgms1's functions provides insights into the mechanisms of related diseases and may offer potential therapeutic targets.

References:

1. Yang, Kai, Luan, Ying-Yi, Wang, Shan, Zhang, Dong-Liang, Yin, Cheng-Hong. 2024. SGMS1 facilitates osteogenic differentiation of MSCs and strengthens osteogenesis-angiogenesis coupling by modulating Cer/PP2A/Akt pathway. In iScience, 27, 109358. doi:10.1016/j.isci.2024.109358. https://pubmed.ncbi.nlm.nih.gov/38544565/

2. Wang, Shiguan, Chen, Shanze, Sun, Jianfeng, Heikenwalder, Mathias, Yuan, Detian. 2023. m6A modification-tuned sphingolipid metabolism regulates postnatal liver development in male mice. In Nature metabolism, 5, 842-860. doi:10.1038/s42255-023-00808-9. https://pubmed.ncbi.nlm.nih.gov/37188818/

3. Chen, Jing, Lewis, Morag A, Wai, Alisa, Ingham, Neil J, Steel, Karen P. 2024. A new mutation of Sgms1 causes gradual hearing loss associated with a reduced endocochlear potential. In Hearing research, 451, 109091. doi:10.1016/j.heares.2024.109091. https://pubmed.ncbi.nlm.nih.gov/39067415/

4. Filippenkov, I B, Dergunova, L V, Rozhkova, A V, Sudarkina, O Yu, Limborska, S A. . PECULIARITIES OF THE STRUCTURE AND EXPRESSION OF HUMAN SPHINGOMYELIN SYNTHASE 1 GENE (SGMS1). In Tsitologiia, 58, 267-71. doi:. https://pubmed.ncbi.nlm.nih.gov/30191692/

5. Han, Shuo, Ye, Xiaolei, Yang, Jintong, Liu, Wei, Li, Hao. 2024. Host specific sphingomyelin is critical for replication of diverse RNA viruses. In Cell chemical biology, 31, 2052-2068.e11. doi:10.1016/j.chembiol.2024.10.009. https://pubmed.ncbi.nlm.nih.gov/39566509/