Dexamethasone Stimulates Luciferase Gene Expression Through the Rat Bone Sialoprotein Gene Promoter in Transgenic Mice

Abstract
Bone sialoprotein (BSP) is expressed by differentiated osteoblasts during the initial formation and mineralization of bone matrix. Studies using transgenic mice harboring 2.7 kb of the rat BSP promoter linked to a luciferase reporter gene have shown luciferase activity in bone and other mineralized tissues while most soft tissues tested expressed a much lower level of the reporter gene. To study regulation of the transgene, mice were administered dexamethasone (dex) by intramuscular injection. After 4 h and 24 h, various tissues were dissected from the treated mice as well as from untreated transgenic littermates. Luciferase assays showed that dex stimulated expression of the transgene significantly. In bone tissues, dex increased the average luciferase activity 1.6- to 11-fold compared with control tissues from untreated transgenic mice. The luciferase activity in lung, liver and kidney remained at a low level and showed no increase with dex treatment. In some animals, however, the luciferase activity in brain and skin was also increased after dex administration. These experiments indicate that a transgene comprising 2.7 kb of the rat BSP promoter linked to a luciferase reporter is regulated in a tissue and developmental stage-dependent manner and that glucocorticoid-induced stimulation of BSP gene expression may be mediated within this region of the promoter.