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Copper utilization in cultured skin fibroblasts of the mottled mouse, an animal model for Menkes' kinky hair syndrome
Author(s) -
Packman S.,
Chin P.,
O'Toole C.
Publication year - 1984
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/bf01805602
Subject(s) - intracellular , menkes disease , cytosol , mutant , copper deficiency , copper , biology , superoxide dismutase , lesion , locus (genetics) , microbiology and biotechnology , biochemistry , chemistry , copper metabolism , pathology , enzyme , medicine , gene , organic chemistry
An animal model for Menkes' kinky hair syndrome is provided by mice mutant at the X‐linked mottled locus. Two mechanisms have been invoked to explain disease manifestations in mottled and in kinky hair syndrome: (i) relative tissue copper deficiencies and corresponding reductions in cuproenzyme activities; or (ii) defective intracellular copper utilization, with impaired intracellular translocation to cuproenzymes or to copper‐dependent processes. We addressed the second possibility through measurements of soluble superoxide dismutase (SOD‐1) in cytosol extracts of confluent mottled (blotchy) cultured skin fibroblasts. At comparable intracellular copper concentrations over a broad range, SOD‐1 specific activities in the mutant cells were not distinguishable from those in controls, or, in some instances, were actually higher. These data suggest that the excess copper anomalously sequestered in a cell expressing the mutation remains available for binding to a cytosolic cuproenzyme. When taken together with data in other systems, the results are consistent with the thesis that the basic lesion in blotchy may primarily affect copper transport or delivery to specific copper transport systems.