Characterization of a murine high-affinity thiamine transporter, Slc19a2

Thiamine-responsive megaloblastic anemia with deafness and diabetes (TRMA) is a rare autosomal recessive disorder of thiamine transport. Previous stud ies have demonstrated that the disease is caused by mutations in the SLC19A 2 gene encoding a high-affinity thiamine transporter. We hypothesize that t hiamine transport, mediated by SLC19A2, plays a role in the development and or maintenance of several organ systems, in particular the erythropoietic, auditory, and glucose homeostasis systems. To investigate the transporter further, we cloned the murine Slc19a2 locus and characterized the resulting protein. Murine Slc19a2 is a 498 amino acid protein, with 12 predicted tra nsmembrane domains. The gene spans similar to 13kb with 6 exons, structural ly identical to that of the human homolog. We localized the Slc19a2 gene to mouse chromosome 1, a region syntenic to human chromosome 1q23 that contai ns the TRMA locus. Transient expression of Slc19a2 in HEK293T cells resulte d in specific uptake of [H-3] thiamine, confirming a thiamine transporter f unction. Western blot analysis of mouse tissues reveals a wide distribution of Slc19a2 protein. Immunohistochemistry studies indicate that Slc19a2 is expressed on the cell surface and intracellularly, and is specifically loca lized to a subpopulation of cells in cochlea, small intestine, and pancreas . (C) 2001 Academic Press.