Mutations in the dystrophin gene1 (DMD) and in genes
encoding several dystrophin-associated proteins result in Duchenne and other
forms of muscular dystrophy2. -Dystroglycan (Dg) binds
to laminins in the basement membrane surrounding each myofibre and docks with -Dg,
a transmembrane protein, which in turn interacts with dystrophin or utrophin
in the subplasmalemmal cytoskeleton. - and -Dgs are thought to
form the functional core of a larger complex of proteins extending from the
basement membrane to the intracellular cytoskeleton, which serves as a superstructure
necessary for sarcolemmal integrity2. Dgs have also been implicated
in the formation of synaptic densities of acetylcholine receptors (AChRs)
on skeletal muscle3,
4. Here we report that chimaeric mice generated
with ES cells targeted for both Dg alleles have skeletal muscles essentially
devoid of Dgs and develop a progressive muscle pathology with changes emblematic
of muscular dystrophies in humans. In addition, many neuromuscular junctions
are disrupted in these mice. The ultrastructure of basement membranes and
the deposition of laminin within them, however, appears unaffected in Dg-deficient
muscles. We conclude that Dgs are necessary for myofibre survival and synapse
differentiation or stability, but not for the formation of the muscle basement
membrane, and that Dgs may have more than a purely structural function in
maintaining muscle integrity.
-Dystroglycan (Dg) binds
to laminins in the basement membrane surrounding each myofibre and docks with 
-Dg,
a transmembrane protein, which in turn interacts with dystrophin or utrophin
in the subplasmalemmal cytoskeleton. 
