Medical College of Wisconsin
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Targeting and intracellular trafficking of clinically relevant hTHTR1 mutations in human cell lines. Clin Sci (Lond) 2007 Jul;113(2):93-102



Pubmed ID




Scopus ID

2-s2.0-34447512789   12 Citations


The micronutrient thiamine is required for normal growth and development of human tissues, and is accumulated into cells through the activity of plasma membrane thiamine transporters, e.g. hTHTR1 (human thiamine transporter 1). Recent genetic evidence has linked mutations in hTHTR1 with the manifestation of TRMA (thiamine-responsive megaloblastic anaemia), a condition also associated with diabetes mellitus, sensorineural deafness and retinal disorders. To examine how mutations in hTHTR1 impair thiamine accumulation, we have investigated the targeting and functional properties of several different hTHTR1 mutants in human cell lines derived from epithelia relevant to thiamine absorption or tissues implicated in TRMA pathology. These constructs encompassed two newly identified point mutations (P51L and T158R) and two truncations of hTHTR1 identical with those found in TRMA kindreds (W358X and Delta383fs). Our results reveal a spectrum of mutant phenotypes, underlining that TRMA can result from decreased thiamine transport activity underpinned by changes in hTHTR1 expression levels, cellular targeting and/or protein transport activity.

Author List

Subramanian VS, Marchant JS, Said HM


Jonathan S. Marchant PhD Chair, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Anemia, Megaloblastic
Cell Line
DNA Mutational Analysis
Diabetes Mellitus
Flow Cytometry
Membrane Transport Proteins
Microscopy, Confocal
Point Mutation
Protein Transport
Reverse Transcriptase Polymerase Chain Reaction
Thiamine Deficiency
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a