SELECTIVE EXPRESSION OF A SKI TRANSGENE AFFECTS IIB PAST MUSCLES AND SKELETAL STRUCTURE

The expression of a ski transgene in the hind leg muscles of mice foll ows a spatial and temporal pattern reminiscent of the pattern of myoge nic development, Anterior muscles, which are formed earliest during de velopment, are also the first muscles to express ski mRNA. Muscles der ived from the posterior muscle group, formed later during development, exhibit delayed expression of ski mRNA. In addition, there is regiona l 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 con tain a lower percentage of type IIb fibers and lower ATPase activity, The soleus, a slow muscle composed predominantly of type I fibers, exp resses low ATPase activity and contains much lower levels of ski mRNA, mRNA from the ski transgene is also expressed at high levels in the o steocytes of the leg bones of 15-day and older transgenic mice. High l evels of Ski protein is present in the osteocytes of the leg bones, sk i 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 fractur es were found in several bones in the ski transgenic mice, (C) 1996 Wi ley-Liss, Inc.