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Slc19a2 and Slc19a3 knockout mouse models have been generated to evaluate intestinal absorption of thiamine in vitro and in vivo [62]. Slc19a3 ^−/− mice are viable and fertile, but a noticeable change in gross phenotype occurs around 1 year of age. In particular, the mice exhibit progressive wasting 2–3 months prior to a premature death at 1 year of age. Chronic inflammation in hepatic parenchyma and renal cortex is observed in the mice. Notably, thiamine plasma levels in Slc19a3 ^−/− mice are significantly lower than sex‐matched wild‐type mice, reflecting reduced thiamine absorption. In contrast, similar experiments in Slc19a2 ^−/− mice revealed no difference in plasma thiamine levels compared to wild‐type littermates [63].

Slc19a2 knockout mouse models serve as experimental models of TRMA. Homozygous Slc19a2 ^−/− mice are physiologically normal when fed standard chow, but develop sensorineural deafness, megaloblastosis, and diabetes mellitus with reduced insulin secretion and an enhanced response to insulin when fed a thiamine‐deficient diet. Erythrocytes from Slc19a2 ^−/− mice lack the high‐affinity component of thiamine transport. Furthermore, bone marrow samples from thiamine‐deficient Slc19a2 ^−/− mice are abnormal, with megaloblastosis affecting the erythroid, myeloid, and megakaryocyte lines. All aspects of the TRMA phenotype in Slc19a2 ^−/− mice are reversible with doses of thiamine [63].

Pmat ^−/− mice are viable and fertile with no physiologic abnormalities. Further, no significant differences in standard blood chemical measurements are observed between WT and KO mice. Whole brain expression of functionally related transporters (Sert, Dat, Net, Oct3) is not changed by knockout of Pmat, and choroid plexus size and morphology is similar between Pmat ^+/+ and Pmat ^−/− mice [64]. Some studies have observed subtle, sex‐specific phenotypic changes in behavior in Pmat ^−/− mice [65, 66].