PABP2 polyalanine tract expansion causes intranuclear inclusions in oculopharyngeal muscular dystrophy

Oculopharyngeal muscular dystrophy is caused by expansion of a (GCG)(n) tri nucleotide repeat in the poly(A) binding protein 2 (PABP2) gene. The pathol ogical hallmark of oculopharyngeal muscular dystrophy is the accumulation o f intranuclear inclusions in muscle fibers. To test whether the polyalanine expansion of PABP2 directly leads to the formation of the nuclear aggregat es, both normal and expanded PABP2 cDNAs were expressed in COS-7 cells. We find that expression of mutated PABP2 protein is sufficient for its accumul ation as intranuclear inclusions.