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 studies have demonstrated that the disease is caused by mutations in the SLC19A2 gene encoding a high-affinity thiamine transporter. We hypothesize that thiamine 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 transmembrane domains. The gene spans approximately 13kb with 6 exons, structurally identical to that of the human homolog. We localized the Slc19a2 gene to mouse chromosome 1, a region syntenic to human chromosome 1q23 that contains the TRMA locus. Transient expression of Slc19a2 in HEK293T cells resulted in specific uptake of [3H] thiamine, confirming a thiamine transporter function. 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 localized to a subpopulation of cells in cochlea, small intestine, and pancreas.

A novel mutation in the SLC19A2 gene in a Tunisian family with thiamine-responsive megaloblastic anaemia, diabetes and deafness syndrome.

Thiamine-responsive megaloblastic anaemia (TRMA) syndrome with diabetes and deafness was found in two patients from a Tunisian kindred. The proband was homozygous for a novel mutation, 287delG, in the high-affinity thiamine transporter gene, SLC19A2. We demonstrated that fibroblasts from this patient exhibited defective thiamine transport. These data confirm that the SLC19A2 gene is the high-affinity thiamine carrier and that this novel mutation is responsible for TRMA syndrome.

Thiamine-responsive megaloblastic anemia syndrome: a disorder of high-affinity thiamine transport.

Thiamine-responsive megaloblastic anemia (TRMA) syndrome (OMIM No. 249270) comprises a distinctive triad of clinical features: megaloblastic anemia with ringed sideroblasts, diabetes mellitus, and progressive sensorineural deafness. The TRMA gene has been mapped and cloned. Designated "SLC19A2" as a member of the solute carrier gene superfamily, this gene is mutated in all TRMA kindreds studied to date. The product of the SLC19A2 gene is a membrane protein which transports thiamine (vitamin B1) with sub-micromolar affinity. Cells from TRMA patients are uniquely sensitive to thiamine depletion to the nanomolar range, while pharmacologic doses of vitamin B1 ameliorate the anemia and diabetes. Here we review the current status of studies aimed at understanding the pathophysiology of this unique transport defect.

The gene mutated in thiamine-responsive anaemia with diabetes and deafness (TRMA) encodes a functional thiamine transporter.

Thiamine-responsive megaloblastic anaemia with diabetes and deafness (TRMA; MIM 249270) is an autosomal recessive disease thought to be due to a defect in thiamine (vitamin B1) transport. Pharmacological doses of thiamine correct the anaemia, and in some cases improve the diabetes, although progressive sensorineural deafness is irreversible. Previous studies localized the TRMA gene to a 4-cM region on chromosome 1q23.3 (ref. 5), and fine-mapping has recently narrowed that region further. We have previously demonstrated that fibroblasts from people with TRMA lack high-affinity thiamine transport. Expression of a gene encoding a known yeast thiamine transporter, THI10 (refs 8-10), in TRMA mutant cells prevents apoptotic cell death in thiamine-depleted medium. On the basis of these studies, we hypothesized that a defective thiamine transporter causes TRMA. We undertook a candidate gene approach to identify putative thiamine transporters in the 1q23.3 critical region. Here we present evidence that the gene SLC19A2 (for solute carrier family 19 (thiamine transporter), member 2) encodes the first known mammalian thiamine transporter, which we designate thiamine transporter-1 (THTR-1).

Annulate lamellae in phloem cells of virus-infected Sonchus plants.

The occurrence of annulate lamellae (AL) in differentiating phloem of Sonchus oleraceus (Compositae) singly infected with sowthistle yellow vein virus (SYVV) and doubly infected with a combination of SYVV and beet yellow stunt virus is documented by electron microscopy. Cell types in which AL were found were immature sieve elements and phloem parenchyma cells. AL were found only in cells that also contained SYVV particles although a direct association between the virus and AL was not apparent. The substructure of the AL and the relationships between the AL and the nuclear envelope and endoplasmic reticulum are similar to those reported in other descriptions of this organelle in the literature. This report appears to be the first one concerning the association of AL with a plant virus disease.