Tilson M D, Davis G
Surgery. 1983 Aug;94(2):134-41.
A spontaneously aneurysm-prone mouse has a mutation on the X chromosome, which results in an abnormality of copper metabolism. A deficiency of the copper metalloenzyme, lysyl oxidase, results in a deficiency of lysyl-derived cross-linkages in collagen and elastin. Homology of the X chromosome suggests that this model may be relevant to the human abdominal aortic aneurysm (AAA). The present studies on skin from eight AAA patients suggest that copper deficiency occurs in humans, by comparison to skin of paired control subjects with atherosclerotic occlusive disease of the aorta. The lysyl-derived cross-linkage pyridinoline (or some compound with similar ion exchange elution characteristics) is also deficient in patients with AAA; while there is an excess of one of the cross-linkage precursors, hydroxylysine. In addition, the fluorescent properties of hydrolysates of skin from the patients with AAA differ from those of the controls, suggesting that simple biochemical markers might be defined on the basis of these differences in the future. These experiments support the hypothesis that the mouse model is relevant to the disease as it occurs in humans.
一种自发易患动脉瘤的小鼠在X染色体上有一个突变,这导致铜代谢异常。铜金属酶赖氨酰氧化酶的缺乏导致胶原蛋白和弹性蛋白中赖氨酰衍生的交联缺乏。X染色体的同源性表明,该模型可能与人类腹主动脉瘤(AAA)相关。目前对8例AAA患者皮肤的研究表明,与患有主动脉粥样硬化闭塞性疾病的配对对照受试者的皮肤相比,人类存在铜缺乏。AAA患者中赖氨酰衍生的交联吡啶啉(或具有类似离子交换洗脱特性的某些化合物)也缺乏;而交联前体之一羟赖氨酸过量。此外,AAA患者皮肤水解产物的荧光特性与对照组不同,这表明未来可能根据这些差异定义简单的生化标志物。这些实验支持了小鼠模型与人类发生的该疾病相关的假说。