Rigon Laura, Kucharowski Nicole, Eckardt Franka, Bauer Reinhard
Molecular Developmental Biology Unit, Life & Medical Sciences Institute (LIMES), University of Bonn, Carl-Troll-Straße 31, 53115 Bonn, Germany.
Fondazione Istituto di Ricerca Pediatrica "Città della Speranza", Corso Stati Uniti 4, 35127 Padova, Italy.
Life (Basel). 2020 Oct 30;10(11):263. doi: 10.3390/life10110263.
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.
II型粘多糖贮积症（MPS II）是一种溶酶体贮积病，由于溶酶体酶艾杜糖醛酸2-硫酸酯酶（IDS）缺乏，导致糖胺聚糖硫酸乙酰肝素和硫酸皮肤素在所有器官和组织中蓄积。其具有重要的临床特征，严重形式伴有严重的神经受累。然而，关于MPS II的神经发病机制几乎一无所知。为了解决这个问题，我们通过RNA干扰（RNAi）方法在果蝇中建立了一种普遍存在的、神经元和神经胶质细胞特异性敲低模型。该基因的敲低导致该基因表达和酶活性显著降低。然而，糖胺聚糖蓄积、存活率、分子标志物（）和运动行为均未受到影响。即使IDS活性大幅降低，其仍足以防止MPS II RNAi果蝇出现病理表型。因此，MPS II模型需要完全消除酶活性。
