COPPER-METABOLISM IN MOTTLED MOUSE MUTANTS - COPPER CONCENTRATIONS IN TISSUES DURING DEVELOPMENT
COPPER-METABOLISM IN MOTTLED MOUSE MUTANTS - COPPER CONCENTRATIONS IN TISSUES DURING DEVELOPMENT
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DOI：
10.1042/bj1800597
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发表时间：
1979-01-01
影响因子：
4.1
通讯作者：
DANKS, DM
中科院分区：
文献类型：
--
作者：
CAMAKARIS, J;MANN, JR;DANKS, DM
在子宫内发育最后一天、出生后第1天和11日龄时，记录了受x连锁斑驳突变影响的雌性杂合子和雄性小鼠各器官的Cu含量。有缺陷的胎盘转移铜在子宫和出生后肠铜吸收更明显的缺陷。一旦被吸收，铜在身体组织中的分布也不正常。该突变导致肾、肠粘膜和睾丸中铜的异常积聚，而肝脏、脑、血浆和大多数其他器官的铜浓度降低。肠道对铜的吸收不良伴随着在肠粘膜细胞中异常量的金属积累。从十二指肠到回肠，粘膜和肠内铜含量逐渐升高。上肠吸收缺陷，随之而来的腔内铜浓度进行性增加和回肠胞饮症似乎可以解释这些发现。放射性同位素研究消除了铜在胆汁或肠粘膜中过量排泄的可能性。由于所进行的研究处于不同的发展阶段，因此很难将其与Menkes综合征患者的研究结果进行详细的比较，但总的来说，结果似乎非常令人满意。这些差异可能可以用已知的物种差异来解释。所有的研究结果都符合一个假设，即基本缺陷涉及到铜在受损组织（如肾、肠粘膜和胎盘）细胞中的积累和保留。
The Cu content of various organs of brindled female heterozygotes and male mice affected by the X-linked mottled mutation are documented at the last day of intrauterine development, at 1 day after birth and at 11 days of age. Defective placental transfer of Cu in utero and an even more marked defect in intestinal absorption of copper after birth are indicated. There is also an abnormal distribution of Cu among the tissues of the body once it is absorbed. The mutation produces abnormal accumulation of Cu in kidney, gut mucosa and testis, whereas liver, brain, plasma and most other organs show diminished Cu-concentrations. The intestinal malabsorption of Cu is accompanied by accumulation of abnormal amounts of the metal in the intestinal-mucosa cells. Cu concentrations in mucosa and luminal contents rise progressively from duodenum to ileum. Defective upper-intestinal absorption, consequent progressive increase in luminal copper concentration and pinocytosis in the ileum would seem to explain the findings. Radioisotopic studies eliminated the possibility of excessive excretion of Cu in bile or across the intestinal mucosa. Detailed comparison with findings in humans with Menkes'' syndrome is difficult because of the different stages of development at which the studies have been performed, but the results seem in general to conform very satisfactorily. Those differences seen are probably explicable by known species differences. All the findings are in accord with a hypothesis that the basic defect involves accumulation and retention of Cu in the cells of affected tissues such as kidney, gut mucosa and placenta.