Sgms1-flox 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, determining its participation in regulating intracellular vesicular transport, cholesterol metabolism, cell proliferation, apoptosis, etc [4].

In mice, the Sgms1tm1b allele, with exon 7 knocked out, led to a complete lack of detectable Sgms1 transcript in the inner ear. Sgms1tm1b homozygotes initially had normal auditory brainstem response thresholds but then experienced progressive hearing loss, along with a reduced endocochlear potential [3]. Overexpressing Sgms1 could counteract the abnormality caused by Mettl3 deficiency in the liver, which was characterized by toxic ceramide accumulation, mitochondrial damage, and elevated endoplasmic reticulum stress [2]. Also, SGMS1 addition accelerated mesenchymal stem cell (MSC) osteogenic differentiation, while its silencing suppressed this process. SGMS1 overexpression inhibited ceramide and promoted sphingomyelin levels, enhancing phosphorylated Akt, Runx2, and VEGF levels, and promoting osteogenic-angiogenic coupling [1].

In conclusion, Sgms1 is crucial for multiple biological processes. Its knockout mouse models have revealed its role in hearing function, post-natal liver development, and osteogenic-angiogenic coupling. Understanding Sgms1 through these models provides insights into related disease mechanisms such as hearing loss, liver development disorders, and skeletal dysplasia, potentially guiding the development of therapeutic strategies.