Myoferlin is a novel
protein of unknown function with high homology to
dysferlin, the gene mutations of which cause
limb girdle muscular dystrophy type 2B and
Miyoshi myopathy. The myoferlin gene seems to be a candidate for the modifier, and because of the high homology to
dysferlin myoferlin may work as a compensator for the absence of
dysferlin in
dysferlinopathy. This hypothesis is based on the observation that
utrophin, which has 80% homology with
dystrophin, is overexpressing in the
dystrophin deficient myofibers. To test this hypothesis, we investigated the myoferlin expression by immunoblot and immunohistochemical analysis in muscles of five patients with
dysferlinopathy. For this aim, we generated a myoferlin specific antibody that does not cross react with
dysferlin, and performed the immunoblot, immunohistochemical and immunoelectron microscopic studies. Immunohistochemical analysis showed that the
antibodies against myoferlin and
dysferlin clearly stained the normal human myofiber surface membranes. The electron microscopy of single immunogold labeled samples for myoferlin showed the presence of the molecular signal along the normal muscle cell membrane. Immunoblot analysis showed that the intensity of 230-kDa myoferlin band of
dysferlinopathy muscle extracts was similar to that of normal muscle extracts. The immunostaining of
dysferlinopathy muscles with anti-myoferlin antibody revealed a weak immunoreactivity along the muscle cell surface. Thus, the compensatory overexpression of myoferlin was not detected in muscles with
dysferlinopathy.