Nabarra B, Casanova M, Paris D, Nicole A, Toyama K, Sinet P M, Ceballos I, London J
U.345 INSERM, Hôpital Necker, Paris, France.
Lab Invest. 1996 Mar;74(3):617-26.
It has been suggested that the overexpression of copper-zinc superoxide dismutase (SOD-1) in Down's syndrome (DS) patients may be involved in expression of some of the phenotypic characteristics observed in these patients. To explore the possible role of SOD-1 overexpression in the premature thymic involution and immunologic disorders observed in DS patients, transgenic mice overexpressing the human SOD-1 gene have been generated and their thymuses have been studied at the ultrastructural level. Our observations show premature involution of the thymus in SOD-1 transgenic mice, with a strong modification of the thymic microenvironment starting at approximately 3-4 months of age. The thymic microenvironment in 7-month-old transgenic mice is similar to that observed in 20-month-old control mice. We suggest that these results are consistent with the role of SOD-1 overexpression in the early thymic involution observed in DS patients. These transgenic mice provide an interesting model to investigate the deleterious effect of increased dosage of some chromosome 21 genes such as SOD-1 in the pathogenesis of DS.
有人提出，唐氏综合征（DS）患者体内铜锌超氧化物歧化酶（SOD-1）的过度表达可能与这些患者所观察到的一些表型特征的表达有关。为了探究SOD-1过度表达在DS患者中观察到的胸腺过早退化和免疫紊乱中可能发挥的作用，已培育出过度表达人SOD-1基因的转基因小鼠，并在超微结构水平上对其胸腺进行了研究。我们的观察结果显示，SOD-1转基因小鼠的胸腺过早退化，从大约3 - 4个月大时开始，胸腺微环境发生了强烈改变。7个月大的转基因小鼠的胸腺微环境与20个月大的对照小鼠所观察到的相似。我们认为，这些结果与SOD-1过度表达在DS患者中观察到的早期胸腺退化中的作用是一致的。这些转基因小鼠为研究21号染色体上某些基因（如SOD-1）剂量增加在DS发病机制中的有害作用提供了一个有趣的模型。
