title: Alteration of copper physiology in mice overexpressing the human Menkes protein ATP7A.
abstract: The Menkes protein (ATP7A) is defective in the Cu deficiency disorder Menkes disease and is an important contributor to the maintenance of physiological Cu homeostasis. To investigate more fully the role of ATP7A, transgenic mice expressing the human Menkes gene ATP7A from chicken beta-actin composite promoter (CAG) were produced. The transgenic mice expressed ATP7A in lung, heart, liver, kidney, small intestine, and brain but displayed no overt phenotype resulting from expression of the human protein. Immunohistochemical analysis revealed that ATP7A was found primarily in the cardiac muscle, smooth muscle of the lung, distal tubules of the kidney, intestinal enterocytes, and patches of hepatocytes, as well as in the hippocampus, cerebellum, and choroid plexus of the brain. In 60-day- and 300-day-old mice, Cu concentrations were reduced in most tissues, consistent with ATP7A playing a role in Cu efflux. The reduction in Cu was most pronounced in the hearts of older T22#2 females (24%), T22#2 males (18%), and T25#5 females (23%), as well as in the brains of 60-day-old T22#2 females and males (23% and 30%, respectively).
authors.affiliation: Centre for Cellular and Molecular Biology, School of Life and Environmental Sciences, Deakin University, Burwood, Victoria 3052, Australia.
authors.forename: Bi-Xia
authors.initials: BX
authors.lastname: Ke
authors.forename: Roxana M
authors.initials: RM
authors.lastname: Llanos
authors.forename: Magali
authors.initials: M
authors.lastname: Wright
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Deal
authors.forename: Julian F B
authors.initials: JF
authors.lastname: Mercer
mesh_terms: D000199:Actins / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000096:biosynthesis*; D000818:Animals; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000096:biosynthesis*; D002645:Chickens; D003300:Copper / Q000378:metabolism / Q000502:physiology*; D000073840:Copper-Transporting ATPases; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D013054:Spectrophotometry, Atomic; D014018:Tissue Distribution
chemical_list: D000199:Actins; D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases