DOES UTROPHIN EXPRESSION IN MUSCLES OF MDX MICE DURING POSTNATAL-DEVELOPMENT FUNCTIONALLY COMPENSATE FOR DYSTROPHIN DEFICIENCY

We correlated utrophin expression with the physiopathological course i n mdx mice. Evolution of the pathology was assessed by monitoring expr ession of developmental MHC in mdx mice versus control. Utrophin expre ssion is detected by dystrophin/utrophin cross-reacting antibodies and can only be evaluated in mdx mouse muscles (in absence of dystrophin) . This protein was expressed at the periphery of all myotubes and myof ibers during the first postnatal week. It began declining in fast musc les before the third week and disappeared from the soleus between the 3rd and the 4th week. The decrease was concomitant with a sudden degen erative/regenerative process affecting slow muscle earlier and more ma ssively than fast muscles. The pathological process became stable in a ll muscle types (except the diaphragm), with greater utrophin expressi on in the soleus. These results in mdx mice along with observed utroph in expression in severely affected DMD patients suggest that overexpre ssion of utrophin is not enough to explain the stability of regenerate d fibers in mdx mice.