Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (17)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Oishi, K.
Right arrow Articles by Gelb, B. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Oishi, K.
Right arrow Articles by Gelb, B. D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2002, Vol. 11, No. 23 2951-2960
© 2002 Oxford University Press

Targeted disruption of Slc19a2, the gene encoding the high-affinity thiamin transporter Thtr-1, causes diabetes mellitus, sensorineural deafness and megaloblastosis in mice

Kimihiko Oishi1,2, Susanna Hofmann3, George A. Diaz1,2, Tartania Brown1,2, Deepa Manwani1, Lily Ng2, Randy Young4, Helen Vlassara3, Yiannis A. Ioannou2, Douglas Forrest2 and Bruce D. Gelb1,2,*

1Department of Pediatrics, 2Department of Human Genetics and 3Division of Diabetes and Aging, Mount Sinai School of Medicine, New York, NY 10029, USA and 4LabCorp, Research Triangle Park, NC 27709, USA

Received July 25, 2002; Accepted September 3, 2002

Thiamin-responsive megaloblastic anemia syndrome (TRMA) is characterized by diabetes mellitus, megaloblastic anemia and sensorineural deafness. Mutations in the thiamin transporter gene SLC19A2 cause TRMA. To generate a mouse model of TRMA, we developed an Slc19a2 targeting construct using transposon-mediated mutagenesis and disrupted the gene through homologous recombination in embryonic stem cells. Erythrocytes from Slc19a2-/- mice lacked the high-affinity component of thiamin transport. On a thiamin-free diet, Slc19a2-/- mice developed diabetes mellitus with reduced insulin secretion and an enhanced response to insulin. The diabetes mellitus resolved after 6 weeks of thiamin repletion. Auditory-evoked brainstem response thresholds were markedly elevated in Slc19a2-/- mice on a thiamin-free diet, but were normal in wild-type mice treated on that diet as well as thiamin-fed Slc19a2-/- mice. Bone marrows from thiamin-deficient Slc19a2-/- mice were abnormal, with a megaloblastosis affecting the erythroid, myeloid and megakaryocyte lines. Thus, Slc19a2-/- mice have provided new insights into the TRMA disease pathogenesis and will provide a tool for studying the role of thiamin homeostasis in diabetes mellitus more broadly.

* To whom correspondence should be addressed at: Departments of Pediatrics and Human Genetics, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1498, New York, NY 10029, USA. Tel: +1 2126596705; Fax: +1 2128492508; Email: bruce.gelb{at}mssm.edu


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Eur J EndocrinolHome page
A. S Alzahrani, E. Baitei, M. Zou, and Y. Shi
Thiamine transporter mutation: an example of monogenic diabetes mellitus
Eur. J. Endocrinol., December 1, 2006; 155(6): 787 - 792.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
Y. Shima, T. Maeda, S. Aizawa, I. Tsuboi, D. Kobayashi, R. Kato, and I. Tamai
L-arginine import via cationic amino acid transporter CAT1 is essential for both differentiation and proliferation of erythrocytes
Blood, February 15, 2006; 107(4): 1352 - 1356.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. C. Reidling and H. M. Said
Adaptive regulation of intestinal thiamin uptake: molecular mechanism using wild-type and transgenic mice carrying hTHTR-1 and -2 promoters
Am J Physiol Gastrointest Liver Physiol, June 1, 2005; 288(6): G1127 - G1134.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
L. de Jong, Y. Meng, J. Dent, and S. Hekimi
Thiamine Pyrophosphate Biosynthesis and Transport in the Nematode Caenorhabditis elegans
Genetics, October 1, 2004; 168(2): 845 - 854.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.