Impaired intestinal vitamin B1 (thiamin) uptake in thiamin transporter-2-deficient mice.
OBJECTIVE
Intestinal thiamin uptake process is vital for maintaining normal body homeostasis of the vitamin; in vitro studies suggest that both thiamin transporter-1 (THTR-1) and -2 (THTR-2) are involved. Mutations in THTR-1 cause thiamin-responsive megaloblastic anemia, a tissue-specific disease associated with diabetes mellitus, megaloblastic anemia, and sensorineural deafness. However, in patients with thiamin-responsive megaloblastic anemia, plasma thiamin levels are within normal range, indicating that THTR-2 (or another carrier) could provide sufficient intestinal thiamin absorption. We tested this possibility and examined the role of THTR-2 in uptake of thiamin in the intestine of mice.


METHODS
THTR-2-deficient mice were generated by SLC19A3 gene knockout and used to examine intestinal uptake of thiamin in vitro (isolated cells) and in vivo (intact intestinal loops). We also examined intestinal thiamin uptake in THTR-1-deficient mice.


RESULTS
Intestine of THTR-2-deficient mice had reduced uptake of thiamin compared with those of wild-type littermate mice (P < .01); this reduction was associated with a decrease (P < .01) in blood thiamin levels in THTR-2-deficient mice. However, intestinal uptake of thiamin in THTR-1-deficient mice was not significantly different from that of wild-type littermate animals. Level of expression of THTR-1 was not altered in the intestine of THTR-2-deficient mice, but level of expression of THTR-2 was up-regulated in the intestine of THTR-1-deficient mice.


CONCLUSIONS
THTR-2 is required for normal uptake of thiamin in the intestine and can fulfill normal levels of uptake in conditions associated with THTR-1 dysfunction.
Reidling
Jack C
JC
Department of Medical Research, VA Medical Center, Long Beach, California 90822, USA.
Lambrecht
Nils
N
Kassir
Mohammad
M
Said
Hamid M
HM
D000818:Animals; D001522:Behavior, Animal; D001692:Biological Transport; D005786:Gene Expression Regulation; D005838:Genotype; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D026901:Membrane Transport Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D013831:Thiamine / Q000097:blood / Q000378:metabolism*
D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C492292:Slc19a2 protein, mouse; C492290:Slc19a3 protein, mouse; D013831:Thiamine