Biological Trace Element Research

, Volume 136, Issue 2, pp 204–220 | Cite as

Effects of Copper Supplementation on the Structure and Content of Elements in Kidneys of Mosaic Mutant Mice

  • Małgorzata LenartowiczEmail author
  • Renata Windak
  • Grzegorz Tylko
  • Małgorzata Kowal
  • Józefa Styrna


Menkes disease is an effect of ATP7A gene mutation in humans, coding the Cu-ATP-ase which is essential in intestinal copper absorption and its subsequent transfer to circulation. This mutation results in a deficiency of copper in all tissues except the epithelia of intestine and kidney tubules. Subcutaneous injection of copper ions is the main therapy for Menkes patients. Mosaic (Atp7amo-ms) mice closely simulate the situation in Menkes disease. The aim of this study was to evaluate the changes in structure and element content in kidneys of mosaic mice after copper supplementation. Hematoxylin–eosin staining was used to analyze tissue morphology and atomic absorption spectrometry to estimate Cu and Zn content. X-ray microanalysis was performed to measure Na, Mg, P, Cl, and K content in the cells of the proximal and distal tubules. Copper administration lengthened the lifespan of the mutants but led to its high accumulation and results in severe kidney damage. Karyomegalia, necrosis of tubular and Bowman’s capsule epithelium, lesions, and atrophy of glomeruli were observed in the treated mutants. Copper treatment afterwards led to sclerosis of glomeruli and tubules enhanced proliferation of epithelial cells and formation of both polycystic and papillary carcinoma patterns in kidney. We suggest that copper excess may impair the activity of Na+/K+ ATP-ase in renal tubules of ms/− males. The content of Mg, P, and Cl in kidneys in mutants was also changed after copper administration.


Copper metabolism Renal tubules disease Renal necrosis Atp7a gene 



The authors are grateful to Professor Henryk Kozłowski, University of Wrocław, Poland, for the critical reading of the manuscript. This work was supported by grant DS/BiNoZ/IZ/775/2008.


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Copyright information

© Humana Press Inc. 2009

Authors and Affiliations

  • Małgorzata Lenartowicz
    • 1
    Email author
  • Renata Windak
    • 1
  • Grzegorz Tylko
    • 2
  • Małgorzata Kowal
    • 1
  • Józefa Styrna
    • 1
  1. 1.Department of Genetics and Evolution, Institute of ZoologyJagiellonian UniversityKrakówPoland
  2. 2.Department of Cytology and Histology, Institute of ZoologyJagiellonian UniversityKrakówPoland

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