Transgenic mice overexpressing tartrate-resistant acid phosphatase exhibitan increased rate of bone turnover

Tartrate-resistant acid phosphatase (TRAP) is a secreted product of osteocl asts and a lysosomal hydrolase of some tissue macrophages, To determine whe ther TRAP expression is rate-limiting in bone resorption, we overexpressed TRAP in transgenic mice by introducing additional copies of the TRAP gene t hat contained the SV40 enhancer. In multiple independent mouse lines, the t ransgene gave a copy number-dependent increase in TRAP mRNA levels and TRAP activity in osteoclasts, macrophages, serum, and other sites of normal low -level expression (notably, liver parenchymal cells, kidney mesangial cells , and pancreatic secretory acinar cells). Transgenic mice had decreased tra becular bone consistent with mild osteoporosis. Measurements of the bone fo rmation rate suggest that the animals compensate for the increased resorpti on by increasing bone synthesis, which partly ameliorates the phenotype, Th ese mice provide evidence that inclusion of an irrelevant enhancer does not necessarily override a tissue-specific promoter.