title: Hepatic ceruloplasmin gene expression is unaltered in the toxic milk mouse.
abstract: 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.
authors.affiliation: Scobie and Claire Mackinnon Trace Element Laboratory, Murdoch Institute, Royal Children's Hospital, Parkville, Victoria, Australia.
authors.forename: J F
authors.initials: JF
authors.lastname: Mercer
authors.forename: A
authors.initials: A
authors.lastname: Grimes
authors.forename: D M
authors.initials: DM
authors.lastname: Danks
authors.forename: H
authors.initials: H
authors.lastname: Rauch
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002570:Ceruloplasmin / Q000096:biosynthesis / Q000235:genetics*; D003300:Copper / Q000172:deficiency / Q000378:metabolism*; D005260:Female; D005333:Fetus; D015870:Gene Expression; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D003300:Copper; D002570:Ceruloplasmin; D015032:Zinc