Copper transport during lactation in transgenic mice expressing the human ATP7A protein.
Both copper transporting ATPases, ATP7A and ATP7B, are expressed in mammary epithelial cells but their role in copper delivery to milk has not been clarified. We investigated the role of ATP7A in delivery of copper to milk using transgenic mice that over-express human ATP7A. In mammary gland of transgenic mice, human ATP7A protein was 10- to 20-fold higher than in control mice, and was localized to the basolateral membrane of mammary epithelial cells in lactating mice. The copper concentration in the mammary gland of transgenic dams and stomach contents of transgenic pups was significantly reduced compared to non-transgenic mice. The mRNA levels of endogenous Atp7a, Atp7b, and Ctr1 copper transporters in the mammary gland were not altered by the expression of the ATP7A transgene, and the protein levels of Atp7b and ceruloplasmin were similar in transgenic and non-transgenic mice. These data suggest that ATP7A plays a role in removing excess copper from the mammary epithelial cells rather than supplying copper to milk.
Centre for Cellular and Molecular Biology, School of Life and Environmental Sciences, Deakin University, 221 Burwood Hwy, Burwood, Vic. 3125, Australia.
Roxana M
RM
Llanos
Agnes A
AA
Michalczyk
David J
DJ
Freestone
Scott
S
Currie
Maria C
MC
Linder
M Leigh
ML
Ackland
Julian F B
JF
Mercer
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics / Q000502:physiology*; D003300:Copper / Q000032:analysis / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D004847:Epithelial Cells / Q000737:chemistry / Q000201:enzymology; D005260:Female; D015870:Gene Expression; D006720:Homozygote; D006801:Humans; D017136:Ion Transport; D007774:Lactation / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000737:chemistry / Q000166:cytology / Q000201:enzymology*; D051379:Mice; D008822:Mice, Transgenic; D008892:Milk / Q000737:chemistry / Q000201:enzymology
D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases