Transplantation of human myoblasts in SCID mice as a potential muscular model for myotonic dystrophy

Myotonic dystrophy (DM), the most frequent hereditary myopathy in adults, is characterized clinically by muscle weakness, myotonia, and systemic symptoms. Although the specific genetic basis for DM has been established, less is known about the cellular defects responsible for its pleiotropic manifestations. DM pathogenesis studies are presently limited due to the absence of animal models. In the present study, we transplanted myoblasts of DM patients into the Tibialis anterior of Severe Combined Immunodeficient (SCID) mice to determine whether this approach could reproduce the muscular characteristics of DM. One to 4 months after transplantation, a variable number of innervated human muscle fibers, recognized by an antibody specific for the human dystrophin, were found in the transplanted muscles. The CTG expansion was retained in human muscle fibers as determined by Southern blot analysis. Although the histological characteristics of DM were absent in these fibers, electromyographic recording showed typical myotonic discharges in muscles transplanted with DM myoblasts. The specificity of the myotonic runs was demonstrated by its inhibition by apamin, a drug that specifically blocks DM myotonia. We conclude that transplantation of myoblasts from DM patients into SCID mice represents a potential in vivo model for basic studies of this disease.