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Age‐related changes in tissue copper (Cu) and iron (Fe) levels in the Ctr‐1 mouse
Author(s) -
Scherr Rachel Erin,
Chew Michael,
Le Anh,
Keen Carl L.,
UriuAdams Janet Y.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.231.4
Subject(s) - medicine , endocrinology , ceruloplasmin , chemistry , copper deficiency , cerebellum , nitrotyrosine , copper , biology , nitric oxide , nitric oxide synthase , organic chemistry
Ctr‐1, a membrane bound protein, is the primary transporter for Cu into the cell. While Ctr‐1 null mice die early in gestation, heterozygous Ctr‐1 mice are phenotypically normal. We characterized tissue Cu and Fe levels in Ctr‐1 and wildtype (WT) mice at 4 developmentally important timepoints (2, 6, 12 and 18 months). Data show an age‐related decrease in liver Cu levels which was larger in Ctr‐1 mice compared to WT. Similarly, plasma Cu was lower in Ctr‐1 mice compared to WT. Despite these differences, hepatic CuZnSOD and plasma ceruloplasmin activities were similar. Cu concentrations in Ctr‐1 brain regions (medulla pons, cerebrum, cerebellum) were 50% lower than WT at all timepoints. Even with these marked differences, preliminary data showed no evidence of brain nitrosative damage (3‐nitrotyrosine) or altered neurobehavior (rotorod performance) in the Ctr‐1 mice, outcomes which would be expected with dietary Cu deficiency. We suggest that this might be due to a lack of an effect of the Ctr‐1 heterozygosity on Fe metabolism since brain Fe levels are typically low with dietary Cu deficiency, but were unaffected in the Ctr‐1 mice. We propose that the Ctr‐1 model provides a novel approach to studying the specific effects of a deficit of Cu on brain development, relative to the combined effects of deficits of both Cu and Fe that occur with dietary Cu deficiency. (Supported by CHNR 08‐804).