Departamento de Patologia, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil.
J Mol Histol. 2011 Dec;42(6):575-8. doi: 10.1007/s10735-011-9361-3. Epub 2011 Oct 1.
Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of alfa-iduronidase (IDUA), which leads to intralysosomal accumulation of glycosaminoglycans. Some studies have revealed that oxidative stress plays an important role in MPS I. However, the mechanisms by which these alterations occur are still not fully understood. The aim of this study was to analyze genomic instability in blood cells from murine model of MPS I by single cell gel (comet) assay and micronucleus test. The results pointed out genetic damage in blood cells as depicted by the single cell gel (comet) assay results. By contrast, no increase of micronucleated cells were found in mouse blood cells when compared to negative control. Taken together, our results suggest that IDUA deficiency induces genomic damage in blood cells. Certainly, this finding offers new insights into the mechanisms underlying the relation between IDUA deficiency and clinical manifestations that can occur in MPS I patients.
黏多糖贮积症 I 型（MPS I）是由于α-艾杜糖苷酸酶（IDUA）的缺乏引起的，导致溶酶体内糖胺聚糖的积累。一些研究表明氧化应激在 MPS I 中起着重要作用。然而，这些改变发生的机制仍不完全清楚。本研究旨在通过单细胞凝胶（彗星）试验和微核试验分析 MPS I 小鼠模型血细胞中的基因组不稳定性。结果表明单细胞凝胶（彗星）试验结果显示血细胞存在遗传损伤。相比之下，与阴性对照组相比，在小鼠血细胞中未发现微核细胞增加。总之，我们的结果表明 IDUA 缺乏会导致血细胞中的基因组损伤。当然，这一发现为 IDUA 缺乏与 MPS I 患者可能出现的临床表现之间的关系提供了新的见解。
