Structure, expression, and chromosomal localization of the mouse Atox1 gene

Copper trafficking in eukaryotes involves small proteins termed metallochap erones, which mediate copper delivery to specific intracellular sites, Prev ious studies in yeast and human cell lines have suggested that Atox1 plays a critical role in copper delivery to the secretory pathway. In the present study, a mouse Atox1 (mAtox1) cDNA was cloned and shown to encode an open reading frame with 85% amino acid identity to human Atox1. RNA blot analysi s revealed that mAtox1 was expressed as a single transcript in multiple tis sues, and immunoblotting indicated that the relative abundance of mAtox1 mR NA directly correlated with mAtox1 protein. Analysis of the mAtox1 gene loc us revealed a genomic structure with four exons encompassing a total of 14. 5 kb, RFLP and haplotype analyses indicated that the mAtox1 locus was tight ly linked to the Trhr and D15Bir7 loci on mouse chromosome 15, Taken togeth er, these data reveal marked evolutionary conservation of Atox1 structure a nd provide a genomic organization and localization that will aid in the gen etic deciphering of the molecular role of this protein in copper homeostasi s. (C) 2000 Academic Press.