ENHANCED SENSITIVITY OF MDX MICE TO INTRAMUSCULAR INJECTION

Species-specific differences in the inflammatory response, specificall y with regard to mast cells, have been proposed to explain the phenoty pic variation among dystrophin-deficient humans, and mdx mice (Gorospe et al., 1994). To test this hypothesis we have intramuscularly inject ed a mast cell secretogogue into both dystrophin-negative mdr and dyst rophin-positive normal mice. Mast cell activity was determined by meas uring the activity of mast cell tryptase, while creatine kinase activi ty was used to determine the course of muscle damage in vivo. Area of damage around the injection site was measured at autopsy, and used as an indication of relative sensitivity to the secretogogue effect of co mpound 48/80. Mdr mice exhibited more damage in response to intramuscu lar injection than normal control mice. In addition, mdx mice showed a substantial increase in plasma tryptase activity, followed by a large increase in muscle creatine kinase activity. On the other hand, dystr ophin-positive normal controls injected with 48/80 liberated little CK or tryptase activity. These results are consistent with the hypothesi s that species-specific differences in mast cell activity, or sensitiv ity to mast cell products could account for the variation in pathology seen in dystrophin-deficient animals.