Isolation and Characterization of Thiamin-Responsive Megaloblastic Anemia Gene

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 08671176
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 内分泌・代謝学
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: NOSAKA Kazuto Kyoto Pref.Univ.Med., Dept.Biochem., Res.Assistant, 医学部, 助手 (10228314)
• Co-Investigator(Kenkyū-buntansha): NISHIMURA Hiroshi Kyoto Pref.Univ.Med., Dept.Biochem., Assistant Prof., 医学部, 講師 (60117900)
• Project Period (FY): 1996 – 1997
• Keywords: thiamin / thiamin-responsive megaloblastic anemia / thiamin pyrophosphokinase / thiamin transport protein

Research Abstract

Thiamin-responsive megaloblastic anemia (TRMA ; OMIM 249270) is an autosomal recessive disorder defined by the occurrence of megaloblastic anemia, diabetes mellitus, and sensorineural deafness, responding to thiamin treatment. Although the pathophysiology of TRMA remains obscure and the gene for the syndrome has not been identified yet, it is highly possible that thiamin pyrophosphokinase (TPK) or thiamin transport system is a candidate for the aberrant protein. We have already isolated a TPK gene, THI80, from yeast Saccharomyces cerevisiae and also a thi80 mutant strain. Then we tried to isolate the human TPK cDNA by the functional complementation using yeast thi80 strain as the host cell, but we have not obtained the clone. Now we started to map the TRMA gene using positional cloning strategy with Dr.Cohen (Technion-Israel Institute of Technology). On the other hand, we cloned the gene encoding thiamin transport protein, THI10, from S.cerevisiae and a thi10 mutant strain. Using these materials, we are going to try the cloning of the human cDNA of the thiamin transport protein.

Research Products

• [Publications] 野坂 和人: "酵母のチアミンリン酸代謝酵素系の分子遺伝学的研究" ビタミン. 71(3). 109-120 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Enjo, F., Nosaka, K., et al: "Isolation and Characterization of a Thiamin Transport Gene,THI10,from S.cerevisrae" J.Biol.Chem. 272(31). 19165-19170 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nosaka, K: "Molecular Genetics of Thiamin Phosphates Metabolism in Saccharomyces cerevisiae." Vitamins(Japan). 71(3). 109-120 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Enjo, F., Nosaka, K., Ogata, M., Iwashima, A., and Nishimura, H.: "Isolation and Characterization of a Thiamin Transport Gene, THI10, from Saccharomyces cerevisiae." J.Biol.Chem.272(31). 19165-19170 (1997)
  • Description: 「研究成果報告書概要(欧文)」より