Abstract
Summary: The mosaic (Atp7a mo-ms) is an X-linked, lethal mutation in mice. In mosaic mutant males, many clinical features characteristic of defective copper metabolism have been observed and they die at the age of 15 days, exhibiting strongsimilarities to the brindled and macular mutants. About 4% of the mutant males live to sexual maturity and some of them are fertile. In this paper, alterationsin the structure of the kidney from adult mutants are described. Owing to an inherited defect of efflux, copper is accumulated in the kidney of the mutants up to a toxic level and this leads to severe damage of the renal cortex. Pathological changes in the kidney mostly affected the structure of the renal corpuscle and renaltubules.
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REFERENCES
Danks DM (1988) Copper deficiency in humans. Annu Rev Nutr 8: 253–257.
Franchini A, Barbanti E, Bolognani Fantin AM (1991) Effects of lead on hepatocyte ultrastrucure in Carassius carassius (L.) var. auratus. Tissue Cell 23: 893–901.
Garnica AD, Frias JL, Rennert OM (1977) Menkes Kinky Hair syndrome: is it a treatable disorder? Clin Genet 11: 154–161.
George J, Brewer MD (1995) Interactionsof zinc and molybdenum with copper in therapy of Wilson's disease. Nutrition 11: 114–116.
Gitshier J, Motaff B, Reilly D, Wood WI, Fairbrother WJ (1998) Solution structure of the fourth metal-binding domain from the Menkes copper-transporting ATPase. Nature Structural Biology 5: 47–54.
Hummel KP, Richardson FL, Fekete E (1966) Anatomy. In Green EL, ed. Biology of the Laboratory Mouse. New York: McGraw-Hill, 247–307.
Kasama T, Tanaka H (1989) Effects of oral copper administration to pregnant heterozygous brindled mice on fetal viability and copper levels. J Nutr Sci Vitaminol 35: 627–638.
Kirby JB, Danks DM, Legge GJF, Mercer JFB (1998) Analysis of the distribution of Cu, Fe and Zn and other elements in brindled mouse kidney using a scanning proton microprobe. J Inorg Biochem 71: 189–197.
Kodama H, Abe T, Takama M, Takahashi I, Kodama M, Nishimura M (1993) Histochemical localization of copper in the intestine and kidney of macular mice: light and electron microscopic study. J Histochem Cytochem 41: 1529–1535.
Kowal M, Lenartowicz M (2000) Influence of sex-linked mosaic mutation on mouse sperm phenotype. International Conference of Reproductive Biology 9th French-Czech-Slovak Colloquium, Slovak Academy of Sciences, Stara Lesna, 2000.
Koyama M, Kihachiro H, Nozaki M, Shimada M (1993) Copper metabolism in the macular mouse, an animal model for Menke's kinky hair disease: changes in the cytochrome c oxidase activity and copper content in variousorgans after copper administration Biomed Res 14: 57–64.
Lenartowicz M, Sasuła K (2000) Altered copper metabolism in the Mosaic mutant mice. Nutrition Res 10: 1519–1529.
Lenartowicz M, Sasuła K, Zawadowska B (2001) Alterations in kidney morphology in mice with mosaic mutation. Folia Histochem Cytobiol 39: 275–281.
Murata Y, Kodama H, Abe T, et al (1997) Mutations analysis and expression of the mottled gene in the macular mouse model of Menkes disease. Pediatric Res 42: 436–442.
Nicholson JK, Kendal MD, Osborn D (1983) Cadmium and mercury neprotoxicity. Nature 304: 633–635.
Nolan CV, Saikh ZA (1992) Lead nephrotoxicity and associated disorders: biochemical mechanisms. Toxicology 73: 127–146.
Oshio T, Hino M, Krino A, Matsumara C, Fukuda K (1997) Urologic abnormalities in Menkes Kinky Hair disease: report of three cases. J Pediatr Surg 32: 782–784.
Pena MMO, Koch KA, Thiele DJ (1998) Dynamic regulation of copper uptake and detoxification genesin Saccharomyces cerevisiae. Mol Cell Biol 18: 2514–2523.
Pena MMO, Lee J, Thiele DJ (1999) A delicate balance: homeostatic control of copper uptake and distribution. J Nutr 129: 1251–1260.
Pena MMO, Puig S, Thiele DJ (2000) Characterization of the Saccharomyces cervisiae high affinity copper transport. J Biol Chem 275: 33244–33251.
Philips M, Camakaris J, Danks DM (1986) Comparison of copper deficiency states in the murine mutantsblotchy and brindled. Biochem J 283: 177–183.
Philips M, Camakaris J, Danks DM (1991) A comparison of phenotype and copper distribution in blotchy and brindled mutant mice and nutritionally copper deficient controls. Biol Trace Elem Res 29: 11–29.
Prohaska J (1983) Changes in tissue growth, concentration of copper, iron, cytochrome oxidase and superoxide dismutase subsequent to dietary or genetic copper deficiency in mice. J Nutr 113: 2048–2058.
Prohaska J (1997) Neurochemical roles of copper as antioxidant or prooxidant. In Connor JR, ed. Metals and Oxidative Damage in Neurological Disorders. New York: Plenum Press, 57–75.
Shiraishi N, Aono K, Tagauhi T (1988) Copper metabolism in the macular mutant mouse: an animal model of Menkes kinky-hair disease. Biol Neonate 54: 173–180.
Stephenson GF, Chan HM, Cherian MG (1993) Copper-metallothionein from the toxic milk mutant mouse enhances lipid peroxidation initiated by an organic hydroperoxide. Toxicol Appl Pharmacol 125: 90–95.
Strain JJ (1994) Newer aspects of micronutrients in chronic disease: copper. Proc Nutr Soc 53: 583–598.
Styrna J (1977) Analysis of causes of lethality in mice with the Ms (Mosaic) gene. Genet Polon 18: 61–79.
Suzuki K, Nagara H (1981) Brindled mottled mouse: morphological changes of brain and visceral organs in hemizygous males following copper supplementation Acta Neuropathol 55: 251–255.
Suzuki-Kurasaki M, Okabe M, Kurasaki M (1997) Copper-metallothionein in the kidney of macular mice: a model for Menkes disease. J Histochem Cytochem 45: 1493–1501.
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Lenartowicz, M., Kowal, M., Buda-Lewandowska, D. et al. Pathological structure of the kidney from adult mice with mosaic mutation. J Inherit Metab Dis 25, 647–659 (2003). https://doi.org/10.1023/A:1022877130344
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DOI: https://doi.org/10.1023/A:1022877130344