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.