Conditional ablation of the osteoblast lineage in Col2.3 Delta tk transgenic mice

Two transgenic mouse lines were generated with a DNA construct bearing a 2. 3-kilobase (kb) fragment of the rat al type I collagen promoter driving a t runcated form of the herpes thymidine kinase gene (Col2.3 Delta tk). Expres sion of the transgene was found in osteoblasts coincident with other geneti c markers of early osteoblast differentiation. Mice treated with ganciclovi r (GCV) for 16 days displayed extensive destruction of the bone lining cell s and decreased osteoclast number. In addition, a dramatic decrease in bone marrow elements was observed, which was more severe in the primary spongio sum and marrow adjacent to the diaphyseal endosteal bone. Immunostaining fo r transgene expression within the bone marrow was negative and marrow strom al cell cultures developed normally in the presence of GCV until the point of early osteoblast differentiation. Our findings suggest that the early di fferentiating osteoblasts are necessary for the maintenance of osteoclasts and hematopoiesis. Termination of GCV treatment produced an exaggerated res ponse of new bone formation in cortical and trabecular bone. The Col2.3 Del ta tk mouse should be a useful model to define the interrelation between bo ne and marrow elements as well as a model to analyze the molecular and cell ular events associated with a defined wave of osteogenesis on termination o f GCV treatment.