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Gene Review

Atp7a  -  ATPase, Cu++ transporting, alpha polypeptide

Mus musculus

Synonyms: Blo, Copper pump 1, Copper-transporting ATPase 1, MNK, Menkes disease-associated protein homolog, ...
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Disease relevance of Atp7a


Psychiatry related information on Atp7a


High impact information on Atp7a


Chemical compound and disease context of Atp7a


Biological context of Atp7a


Anatomical context of Atp7a

  • Both Atp7a and Atp7b are expressed in glomeruli; however, Atp7b is also seen in the kidney medulla [20].
  • That is, the brindled mutant and patients with classical Menkes disease are severely copper deficient and have profound neurological problems, while OHS patients and the blotchy mouse have a much milder phenotype with predominantly connective tissue defects [21].
  • In this study, in an attempt to understand the basis for the brindled and blotchy phenotypes, the copper transport characteristics and intracellular distribution of the Mnk protein were assessed in cultured cells from these mutants [21].
  • The mottled gene is expressed in all tissues throughout embryogenesis and is particularly strong in the choroid plexuses of the brain [18].
  • Hepatic expression of both toxic milk and mottled is in the parenchyma, as opposed to blood cells [18].

Associations of Atp7a with chemical compounds

  • Atp7a is required for these copper-dependent effects: Hippocampal neurons isolated from newborn Mo(br) mice reveal a marked sensitivity to endogenous glutamate-mediated NMDA receptor-dependent excitotoxicity in vitro, and mild hypoxic/ischemic insult to these mice in vivo results in significantly increased caspase 3 activation and neuronal injury [22].
  • METHODS: Three groups of mice were studied: group I--normal littermates of blotchy mice; group II--untreated blotchy mice; group III--blotchy mice given either propranolol, atenolol, or nadolol [23].
  • With exposure to either a strong (cadmium) or weaker (zinc) inducer of metallothionein, 64Cu accumulation was increased in normal cells, while there was no change from the already elevated level of 64Cu accumulation in blotchy cells.(ABSTRACT TRUNCATED AT 250 WORDS)[4]
  • These data establish that a Menkes-type Cu-transporting ATPase is expressed in rat C6 and PC12 cells and strongly support the hypothesis that both neurons and glia are involved in maintaining Cu homeostasis in the central nervous system [24].
  • Hydrocortisone treatment resulted in increased metallothionein synthesis in liver of mutant mice but had no ameliorative effect on the mottled-brindled disease [25].

Regulatory relationships of Atp7a

  • A light microscopic study of interruptions of the internal elastic lamina (IIEL) showed that they developed in arteries of both Blotchy and control mice but to a greater extent in the Blotchy group where hypertension further increased their incidence [26].

Other interactions of Atp7a


Analytical, diagnostic and therapeutic context of Atp7a


  1. Metallothionein messenger RNA regulation in the mottled mouse and Menkes kinky hair syndrome. Packman, S., Palmiter, R.D., Karin, M., O'Toole, C. J. Clin. Invest. (1987) [Pubmed]
  2. Spontaneous aortic aneurysms in blotchy mice. Andrews, E.J., White, W.J., Bullock, L.P. Am. J. Pathol. (1975) [Pubmed]
  3. Retinal localization and copper-dependent relocalization of the Wilson and Menkes disease proteins. Krajacic, P., Qian, Y., Hahn, P., Dentchev, T., Lukinova, N., Dunaief, J.L. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  4. Trace metal metabolism in cultured skin fibroblasts of the mottled mouse: response to metallothionein inducers. Packman, S., O'Toole, C. Pediatr. Res. (1984) [Pubmed]
  5. Menkes protein contributes to the function of peptidylglycine alpha-amidating monooxygenase. Steveson, T.C., Ciccotosto, G.D., Ma, X.M., Mueller, G.P., Mains, R.E., Eipper, B.A. Endocrinology (2003) [Pubmed]
  6. Biochemical study on the critical period for treatment of the mottled brindled mouse. Fujii, T., Ito, M., Tsuda, H., Mikawa, H. J. Neurochem. (1990) [Pubmed]
  7. Hypothalamic self-stimulation and operant activity in the mottled mutant mouse. Cazala, P., Cardo, B. Brain Res. Bull. (1977) [Pubmed]
  8. Deletion of the promoter region in the Atp7a gene of the mottled dappled mouse. Levinson, B., Packman, S., Gitschier, J. Nat. Genet. (1997) [Pubmed]
  9. A murine model of Menkes disease reveals a physiological function of metallothionein. Kelly, E.J., Palmiter, R.D. Nat. Genet. (1996) [Pubmed]
  10. The LEC rat has a deletion in the copper transporting ATPase gene homologous to the Wilson disease gene. Wu, J., Forbes, J.R., Chen, H.S., Cox, D.W. Nat. Genet. (1994) [Pubmed]
  11. Mutations in the murine homologue of the Menkes gene in dappled and blotchy mice. Mercer, J.F., Grimes, A., Ambrosini, L., Lockhart, P., Paynter, J.A., Dierick, H., Glover, T.W. Nat. Genet. (1994) [Pubmed]
  12. Propranolol stimulates the crosslinking of matrix components in skin from the aneurysm-prone blotchy mouse. Brophy, C.M., Tilson, J.E., Tilson, M.D. J. Surg. Res. (1989) [Pubmed]
  13. Brindled mottled mouse: morphological changes of brain and visceral organs in hemizygous males following copper supplementation. Suzuki, K., Nagara, H. Acta Neuropathol. (1981) [Pubmed]
  14. Long-term clinical experience with a topical retinoid. Thorne, E.G. Br. J. Dermatol. (1992) [Pubmed]
  15. Sequence of a Menkes-type Cu-transporting ATPase from rat C6 glioma cells: comparison of the rat protein with other mammalian Cu-transporting ATPases. Qian, Y., Tiffany-Castiglioni, E., Harris, E.D. Mol. Cell. Biochem. (1998) [Pubmed]
  16. Prenatal determination of obesity, tumor susceptibility, and coat color pattern in viable yellow (Avy/a) mice. The yellow mouse syndrome. Wolff, G.L., Roberts, D.W., Galbraith, D.B. J. Hered. (1986) [Pubmed]
  17. Functional expression of the Wilson disease protein reveals mislocalization and impaired copper-dependent trafficking of the common H1069Q mutation. Payne, A.S., Kelly, E.J., Gitlin, J.D. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  18. Developmental expression of the mouse mottled and toxic milk genes suggests distinct functions for the Menkes and Wilson disease copper transporters. Kuo, Y.M., Gitschier, J., Packman, S. Hum. Mol. Genet. (1997) [Pubmed]
  19. Mutation analysis provides additional proof that mottled is the mouse homologue of Menkes' disease. Reed, V., Boyd, Y. Hum. Mol. Genet. (1997) [Pubmed]
  20. Expression in mouse kidney of membrane copper transporters Atp7a and Atp7b. Moore, S.D., Cox, D.W. Nephron (2002) [Pubmed]
  21. Intracellular localization and loss of copper responsiveness of Mnk, the murine homologue of the Menkes protein, in cells from blotchy (Mo blo) and brindled (Mo br) mouse mutants. La Fontaine, S., Firth, S.D., Lockhart, P.J., Brooks, H., Camakaris, J., Mercer, J.F. Hum. Mol. Genet. (1999) [Pubmed]
  22. Role of the Menkes copper-transporting ATPase in NMDA receptor-mediated neuronal toxicity. Schlief, M.L., West, T., Craig, A.M., Holtzman, D.M., Gitlin, J.D. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  23. Inhibition of aortic aneurysm development in blotchy mice by beta adrenergic blockade independent of altered lysyl oxidase activity. Moursi, M.M., Beebe, H.G., Messina, L.M., Welling, T.H., Stanley, J.C. J. Vasc. Surg. (1995) [Pubmed]
  24. A Menkes P-type ATPase involved in copper homeostasis in the central nervous system of the rat. Qian, Y., Tiffany-Castiglioni, E., Harris, E.D. Brain Res. Mol. Brain Res. (1997) [Pubmed]
  25. Hepatic metallothionein synthesis in neonatal Mottled-Brindled mutant mice. Piletz, J.E., Herschman, H.R. Biochem. Genet. (1983) [Pubmed]
  26. Experimental cerebral aneurysms in the female heterozygous Blotchy mouse. Coutard, M. International journal of experimental pathology. (1999) [Pubmed]
  27. Age-associated activation of epigenetically repressed genes in the mouse. Bennett-Baker, P.E., Wilkowski, J., Burke, D.T. Genetics (2003) [Pubmed]
  28. Coordinate control and variation in X-linked gene expression among female mice. Greenwood, A.D., Southard-Smith, E.M., Galecki, A.T., Burke, D.T. Mamm. Genome (1997) [Pubmed]
  29. Analysis of Mnk, the murine homologue of the locus for Menkes disease, in normal and mottled (Mo) mice. George, A.M., Reed, V., Glenister, P., Chelly, J., Tümer, Z., Horn, N., Monaco, A.P., Boyd, Y. Genomics (1994) [Pubmed]
  30. Molecular basis of the brindled mouse mutant (Mo(br)): a murine model of Menkes disease. Grimes, A., Hearn, C.J., Lockhart, P., Newgreen, D.F., Mercer, J.F. Hum. Mol. Genet. (1997) [Pubmed]
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