Selective expression of a ski transgene affects IIb fast muscles and skeletal structure.

The expression of a ski transgene in the bind leg muscles of mice follows a spatial and temporal pattern reminiscent of the pattern of myogenic development. Anterior muscles, which are formed earliest during development, are also the first muscles to express ski mRNA. Muscles derived from the posterior muscle group, formed later during development, exhibit delayed expression of ski mRNA. In addition, there is regional variation in ski mRNA levels within a particular muscle. Superficial regions of fast muscles, which contain a large percentage of type IIb fibers and have a high ATPase activity, express a higher level of ski mRNA than the deep portions of the same muscles. The deep regions contain a lower percentage of type IIb fibers and lower ATPase activity. The soleus, a slow muscle composed predominantly of type I fibers, expresses low ATPase activity and contains much lower levels of ski mRNA. mRNA from the ski transgene is also expressed at high levels in the osteocytes of the leg bones of 15-day and older transgenic mice. High levels of Ski protein is present in the osteocytes of the leg bones. ski expression appears to cause remodeling of the tibia and fibula. The cross-sectional area of the tibia and fibula of ski transgenic mice is significantly decreased compared to controls. X-rays of the skeletons of ski transgenic mice suggest that the bones of the entire skeleton are thinner than the bones in normal mice. Pathological stress fractures were found in several bones in the ski transgenic mice.