Multiple cellular phenotypes in an insertional mutation in mouse affectingbone development

The 6093 line of transgenic mice exhibits altered bone development as a res ult of an insertional mutation by the transgene. Female transgenic mice sho w a marked kyphosis as early as 2 weeks of age. Vertebrae from female mice have lower total bone area and mineral content than age-matched, gender-mat ched controls, although the bone mineral density is not changed. The femur and tibia exhibit the opposite effect-increased bone area and mineral conte nt. Fluorescent bone label experiments indicated an increased rate of bone mineral deposition in the femur during the early postnatal growth period, a nd bone marrow from femurs of 6093 females had increased numbers of fibrobl ast colony-forming units. Transgenic females also are obese and have altere d thymocyte development, suggesting that the insertional mutation affects m ultiple cell populations. We hypothesize that these phenotypes arise as a r esult of an alteration in the function or developmental potential of a stro mal cell or mesenchymal stem cell.