Expression profile of the copper homeostasis gene, rAtox1, in the rat brain

In humans the regulation of cellular copper homeostasis is essential for pr oper organ development and function. A novel cytosolic protein, named Atox1 , was recently identified in yeast that functions in shuttling intracellula r mononuclear copper [Cu(I)] to copper-requiring proteins. Atox1 and its hu man homolog, hAtox1, are members of an emerging family of proteins termed c opper chaperones that are involved in the maintenance of copper homeostasis . Northern blot analysis demonstrates that Atox1 is widely expressed at var ying levels in a variety of rat tissues including brain. Using in situ hybr idization histochemistry, we characterized the expression profile for the r at homolog of Atox1 (rAtox1) in the normal adult rat brain. There is widesp read expression within the brain that appears to be primarily neuronal. The highest levels of Atox1 message consists of distinct neuronal subtypes tha t are also characterized by their high levels of metals like copper, iron, and zinc, which include the pyramidal neurons of the cerebral cortex and hi ppocampus in addition to the neurons of the locus coeruleus. The high level s of a metal chaperone like Atox1 in subsets of neurons that also sequester metals suggests that Atox1 may be important in maintaining the functionali ty of metal requiring enzymes. A detailed analysis of the restricted expression profile for a novel copper chaperone, rAtox1, is described in the adult rat CNS. Further analysis sho ws that Atox1 expression is associated with neuronal populations that seque ster copper. (C) 1999 IBRO. Published by Elsevier Science Ltd.