Modeling Mucopolysaccharidosis Type II in the Fruit Fly by Using the RNA Interference Approach.

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder that occurs due to the deficit of the lysosomal enzyme iduronate 2-sulfatase (IDS) that leads to the storage of the glycosaminoglycan heparan- and dermatan-sulfate in all organs and tissues. It is characterized by important clinical features and the severe form presents with a heavy neurological involvement. However, almost nothing is known about the neuropathogenesis of MPS II. To address this issue, we developed a ubiquitous, neuronal, and glial-specific knockdown model in by using the RNA interference (RNAi) approach. Knockdown of the gene resulted in a significant reduction of the gene expression and enzymatic activity. However, glycosaminoglycan storage, survival, molecular markers (), and locomotion behavior were not affected. Even strongly reduced, IDS-activity was enough to prevent a pathological phenotype in a MPS II RNAi fruit fly. Thus, a MPS II model requires complete abolishment of the enzymatic activity.