Hepatic metallothionein gene expression in toxic milk mice.
The toxic milk mutation (tx) in mice is an autosomal recessive condition that causes a marked hepatic accumulation of copper in adults and severe copper deficiency in the pups of tx/tx dams. We determined the concentration of metallothionein-I (MT-I) mRNA in mutant and normal animals at various stages of development and following administration of copper and zinc. In two tx/tx males the average MT-I mRNA was 329 molecules/pg RNA compared with 38 molecules/pg in normal animals. In fetal and neonatal animals the concentration of MT-I mRNA was generally the same in normal and mutant mice and was independent of copper status. Copper or zinc administration to 7-d-old pups caused a marked induction of MT-I mRNA. There was an increased response to copper administration in one mutant group, but no clear pattern of hyper-induction of the MT gene in tx/tx animals was demonstrated. The elevation of MT-I mRNA in adult toxic milk mice is likely to be a secondary consequence of copper accumulation and not a primary effect of the mutation, because high MT-I mRNA levels would have been observed in the mutant neonates and fetuses. However, the possibility that the tx mutation causes overexpression of MT in post-weaning animals cannot be excluded by these data. The results also show that copper deficiency has no effect on the fetal or neonatal expression of the MT genes.
Mercer
J F
JF
Scobie and Claire MacKinnon Trace Element Laboratory, Murdoch Institute, Royal Children's Hospital, Parkville, Melbourne, Victoria, Australia.
Grimes
A
A
Rauch
H
H
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D003300:Copper / Q000172:deficiency* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D007774:Lactation; D008099:Liver / Q000378:metabolism*; D008297:Male; D008431:Maternal-Fetal Exchange; D008668:Metallothionein / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008892:Milk; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology
D012333:RNA, Messenger; D003300:Copper; D008668:Metallothionein; D015032:Zinc