• oculopharyngeal muscular dystrophy

This report describes oculopharyngeal muscular dystrophy (OPMD); this disease is typically inherited as an autosomal dominant. The human gene implicated in OPMD is poly(A)-binding protein-1 (PABPN1); the disease has been associated with an expansion of an N-terminal polyalanine tract in the protein (expanded GCG repeat in the gene). There is a single fly ortholog, Dmel\Pabp2, for which classical hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Orthologous genes in invertebrates, including Drosophila, lack a polyalanine tract at the N-terminus. See, also, the human disease model report 'polyalanine diseases' (FBhh0000179).

Multiple different UAS constructs of the human Hsap\PABPN1 gene have been introduced into flies, including wild-type, constructs with an expanded polyalanine tract, and constructs with other mutational lesions. Variant(s) implicated in human disease tested (as transgenic human gene, PABPN1): A2_A11 (GCG)n EXPANSION, (GCG)7; PABPN1 constructs with expansion of the normal 10-alanine repeat to a 17-alanine repeat have been characterized in flies. These models recapitulate key features of the disease, including progressive muscle degeneration and formation of nuclear inclusions. Reduced dosage of endogenous Dmel\Pabp2 ameliorates a wing phenotype produced by expression of the human gene, suggesting some gain-of-function aspects. Phenotypic assays using the human gene have allowed characterization of genetic interactions with candidate fly genes.

Loss-of-function mutations in the Dmel\Pabp2 gene are lethal, typically in the first larval instar. Physical and genetic interactions of Dmel\Pabp2 have been described; see below and in the Pabp2 gene report.

[updated Jul. 2017 by FlyBase; FBrf0222196]