THE HUMAN OSMOREGULATORY NA+ MYO-INOSITOL COTRANSPORTER GENE (SLC5A3)- MOLECULAR-CLONING AND LOCALIZATION TO CHROMOSOME-21/

A human Na+/myo-inositol cotransporter (SLC5A3) gene was cloned; seque ncing revealed a single intron-free open reading frame of 2157 nucleot ides. Containing 718 amino acid residues, the predicted protein is hig hly homologous to the product of the canine osmoregulatory SLC5A3 gene . The SLC5A3 protein is number 3 of the solute carrier family 5 and wa s previously designated SMIT. Using fluorescence in situ hybridization , the human SLC5A3 gene was localized to band q22 on chromosome 21. Ma ny tissues including brain demonstrate gene expression. The inability of a trisomic 21 cell to downregulate expression of three copies of th is osmoregulatory gene could result in increased flux of both myo-inos itol and Na+ across the plasma membrane. The potential consequences in clude perturbations in the cell membrane potential and tissue osmolyte levels. The SLC5A3 gene may play a role in the pathogenesis of Down s yndrome. (C) 1995 Academic Press, Inc.