Trace Metal Metabolism in Cultured Skin Fibroblasts of the Mottled Mouse: Response to Metallothionein Inducers View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1984-12

AUTHORS

Seymour Packman, Cynthia O'Toole

ABSTRACT

ABSTRACT: Menkes' kinky hair syndrome is a lethal Xlinked disorder marked by tissue-specific increases in copper content. An animal model of kinky hair syndrome is provided by mice mutant at the X-linked mottled locus. The basic defect is unknown. In order to discriminate among potential etiologies, we asked whether the expression of the mottled mutation causes abnormalities in the metabolism of trace metals other than copper in hemizygous mottled (blotchy) cultured skin fibroblasts, and whether we can differentiate mutant and normal cells according to their response to metal inducers of metallothionein. Blotchy fibroblasts accumulated up to 12 times more 64Cu than control (littermate) cells, over time and over a range of 64Cu concentrations. A saturable high affinity component to 64Cu accumulation over a fixed time interval was revealed in these studies. While 64Cu uptake kinetics were indistinguishable in mutant and control cells, the patterns of 64Cu exit differed. In both cell types, the rate of release of a rapidly exchangeable fraction of newly acquired 64Cu was similar. However, in mutant cells, a larger fraction of recently accumulated 64Cu is retained. In contrast to the results for 64Cu, accumulation and exit of 65Zn and 109Cd were not distinguishable in mutants and controls. With exposure to either a strong (cadmium) or weaker (zinc) inducer of metallothionein, 64Cu accumulation was increased in normal cells, while there was no change from the already elevated level of 64Cu accumulation in blotchy cells. In contrast, the effects of metal inducers of metallothionein on 65Zn or 109Cd accumulation in mutant cells were indistinguishable from the effects on controls. The present observations reveal that blotchy fibroblasts exhibit normal accumulation and exit of metals other than copper, and evince a differential response to metallothionein inducers, which response is also limited to the accumulation of copper. When considered together with the larger body of data on the kinky hair syndrome and mottled mutation, we infer that the defect in both species resides in the function of a thionein or other protein specifically binding copper; or in an altered transport system specifically affecting copper. More... »

PAGES

1282-1286

Identifiers

URI

http://scigraph.springernature.com/pub.10.1203/00006450-198412000-00011

DOI

http://dx.doi.org/10.1203/00006450-198412000-00011

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1026418829

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/6542992


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