Mercer J F, Grimes A, Danks D M, Rauch H
Scobie and Claire Mackinnon Trace Element Laboratory, Murdoch Institute, Royal Children's Hospital, Parkville, Victoria, Australia.
J Nutr. 1991 Jun;121(6):894-9. doi: 10.1093/jn/121.6.894.
The toxic milk mutation in mice is an autosomal recessive condition that causes a marked hepatic accumulation of copper in the adults, but is also characterized by severe copper deficiency in the pups of toxic dams. To establish whether the mutation affects ceruloplasmin (CP) gene expression, we analyzed the steady state levels of CP mRNA in mutant and normal animals at various stages of development and following administration of copper and zinc. In fetal and neonatal animals, the expression of the CP gene is unaltered by the mutation or the copper deficiency in the pups of mutant dams. Copper and zinc administration to 7-d-old pups caused a significant increase (35%) in CP mRNA in all genotypes. In the adults that had accumulated 600-700 micrograms/g dry wt of copper in the liver, the CP mRNA level was normal, but pregnancy produced two-to fourfold elevation of the mRNA in both normal and mutant females. These results suggest that the toxic milk mutation does not affect the regulation of the CP gene and that the gene is not responsive to copper deficiency, copper administration or copper excess in the liver.
小鼠的毒性乳突变是一种常染色体隐性疾病，会导致成年小鼠肝脏中铜显著蓄积，但毒性母鼠所产幼崽的特征却是严重缺铜。为确定该突变是否影响铜蓝蛋白（CP）基因表达，我们分析了突变型和正常动物在不同发育阶段以及给予铜和锌后CP mRNA的稳态水平。在胎儿和新生动物中，突变或突变型母鼠所产幼崽的铜缺乏均不会改变CP基因的表达。给7日龄幼崽给予铜和锌后，所有基因型的CP mRNA均显著增加（35%）。在肝脏中已蓄积600 - 700微克/克干重铜的成年小鼠中，CP mRNA水平正常，但怀孕会使正常和突变型雌性小鼠的mRNA升高两到四倍。这些结果表明，毒性乳突变不影响CP基因的调控，且该基因对肝脏中的铜缺乏、铜给予或铜过量均无反应。
