Sgms2-flox Mouse

Sgms2, encoding sphingomyelin synthase 2 (SMS2), is an enzyme involved in the production of sphingomyelin (SM), a key lipid component of the plasma membrane. SM metabolism, regulated by Sgms2, is crucial for signal transduction and has important implications in skeletal and neural tissues [1].

Pathogenic heterozygous variants in Sgms2 lead to a spectrum of skeletal conditions. In some families, Sgms2 variants cause childhood-onset osteoporosis with low bone mineral density, sclerotic doughnut-shaped lesions in the skull, or a more severe spondylometaphyseal dysplasia with neonatal fractures, long-bone deformities, and short stature. Some patients also experience neurological manifestations such as peripheral facial nerve palsy. Bone biopsies from affected individuals show defective bone mineralization, altered bone material characteristics, and abnormal osteocyte lacunocanalicular network [1,2,3,4,5].

In conclusion, Sgms2 is essential for sphingomyelin metabolism and plays a critical role in maintaining skeletal homeostasis. Research on Sgms2-related disorders helps to understand the molecular mechanisms underlying early-onset osteoporosis and skeletal dysplasia, potentially guiding the development of targeted therapies for these bone-related diseases.