Effects of copper supplementation on the structure and content of elements in kidneys of mosaic mutant mice

Biol Trace Elem Res. 2010 Aug;136(2):204-20. doi: 10.1007/s12011-009-8533-4. Epub 2009 Oct 15.

Abstract

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 (Atp7a(mo-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Animals
  • Cation Transport Proteins / genetics
  • Copper / administration & dosage
  • Copper / metabolism*
  • Copper / pharmacology*
  • Copper / toxicity
  • Copper-Transporting ATPases
  • Dietary Supplements*
  • Electron Probe Microanalysis
  • Female
  • Kidney / chemistry
  • Kidney / drug effects*
  • Longevity / drug effects
  • Male
  • Menkes Kinky Hair Syndrome / drug therapy
  • Mice
  • Mutation
  • Trace Elements / administration & dosage
  • Trace Elements / metabolism
  • Trace Elements / pharmacology
  • Trace Elements / toxicity

Substances

  • Atp7a protein, mouse
  • Cation Transport Proteins
  • Trace Elements
  • Copper
  • Adenosine Triphosphatases
  • Copper-Transporting ATPases
  • cupric chloride