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1993 Fiscal Year Final Research Report Summary

Analysis of thyroxine-binding globulin (TBG) gene regulation and inherited TGB abnormalities

Research Project

Project/Area Number 04671468
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionNagoya University

Principal Investigator

MORI Yuichi  Nagoya Uni. School of Medicine Assistant Prof., 医学部, 助手 (70230084)

Co-Investigator(Kenkyū-buntansha) OKAMOTO Hideki  Nagoya Uni. School of Medicine Medical staff, 医学部, 医員
Project Period (FY) 1992 – 1993
KeywordsThyroxine-binding globulin / Complete deficiency / Partial deficiency / Excess / Frameshift mutation / Gene screening / Intracellular transport / HNF-1
Research Abstract

1. Complete TGB deficiency in Japanese(TBG-CDJ)has a nucleotide deletion at codon 352 among 395 resulting in the production of C-terminal 22 amino acid truncation due to a frameshift and premature termination. The cDNA of TBG-CDJ was expressed in COS-1 cells. Pulse chase experiment revealed TBG-CDJ was retained in the rough endoplasmic reticulum resulting in complete deficiency in serum.
Gene screening showed 23 Japanese families with TBG-CD had a same mutation TBG-CDJ.
2. Abnormality of X-chromosome inactivation was found in a female TBG-CD patient. She was heterozygous of TBG-CDJ and normal TBG alleles. The latter allele was selectively inactivated.
3. Partial TBG deficiency in Japanese (TBG-PDJ) has a nucleotide substitution at codon 363 replacing normal pro (CCT) with leu (CTT). The TBG-PDJ was expressed in COS-1 cells. lt was revealed that delay of intracellular transport of TBG-PDJ was a cause of partial deficiency. Induction of GRP78, molecular chaperone, was found to participate the transport disorder.
4. Gene duplication was shown in a hereditary TBG excess family by using PCR and HPLC.
5. Human and rat genomic TBG genes were isolated and characterized. Promoter regions of both genes were sequenced and subcloned to CAT or luciferase reporter construct. HNF-1 (hepatocyte nuclear factor 1) binding site was found important fot basal and liver specific expression. Gene expression and serum. TBG were down regulated by corticosterone in rat.

  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Yoshitaka Hayashi: "Human thyroxine-binding globulin gene:complete sequence and transcriptional regulation." Molecular Endocrinology. 7. 1049-1060 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Charles H.Emerson: "Gene expression and serum thyroxine-binding globulin are regulated by adrenal status and corticosterone in the rat." Endocrinology. 133. 1192-1196 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikuo Yamamori: "Gene screening of 23 Japanese families with complete thyroxine-binding globulin deficiency:identification of a nucleotide deletion at codon 352 as a common cause." Endocrine Journal. 40. 563-569 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshitaka Miura: "Sequence of a variant thyroxine-binding globulin(TBG)in a family with partial TBG deficiency in Japanese(TBG-PDJ)." Endocrine Journal. 40. 127-132 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsukasa Noguchi: "Hereditary complete thyroxine-binding globulin deficiency:identification by T3 resin uptake test and DNA analysis." Internal Medicine. 32. 6-9 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kambe Fukushi: "An additional carbohydrate chain in the variant thyroxine-binding globulin(TBG asp-96)impairs its secretion." Molecular Endocrinology. 6. 443-449 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshitaka Miura: "A truncated thyroxine-binding globulin due to a frameshift mutation is retained within the rough endoplasmic reticulum." The Journal of Clinical Endocrinology & Metabolism. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kyoko Takeda: "Gene screening in Japanese families with thyroxine binding globulin complete deficiency demonstrates that a nucleotide deletion at codon 352 may be a rase specific mutation." Clinical Endocrinology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 森 祐一: "TBG異常症とTBG遺伝子" Medicina. 31. 302-305 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 三浦義孝: "日本人のTBG完全欠損症(TBG-CDJ)の発症機序に関する研究" 名古屋大学環境医学研究所年報. 44. 161-165 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 妹尾久雄: "遺伝性サイロキシン結合グロブリン(TBG)異常症" ホルモンと臨床. 40. 1221-1227 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshitake Miura et al.: "A truncated thyroxine-binding globulin due to a frameshift mutation is retained within the rough endoplasmic reticulum" J Clin Endocrinol Metab. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshitake Hayashi et al.: "Human thyroxine-binding globulin gene : complete sequence and transcriptional regulation" Molecular Endocrinology. 7. 1049-1060 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Charles H.Emerson et al.: "Gene expression and serum thyroxine-binding globulin are regulated by adrenal status and corticosterone in the rat" Endocrinology. 133. 1192-1196 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikuo Yamamori et al.: "Gene screening of 23 Japanese families with complete thyroxine-binding globulin deficiency : identification of a nucleotide deletion at codon 352 as a common cause" Endocrine Journal. 40. 563-569 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshitake Miura et al.: "Sequence of a variant thyroxine-binding globulin (TBG) in a family with partial TBG deficiency in Japanese (TBG-PDJ)" Endocrine Journal. 40. 127-132 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsukasa Noguchi et al.: " Hereditary complete thyroxine-binding globulin deficiency : identification by T3 resin uptake test and DNA analysis" Internal medicine. 32. 6-9 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kyoto Takeda et al.: "Gene screening in Japanese families with thyroxine binding globulin complete deficiency demonstrates that a nucleotide deletion at codon 352 may be a rase specific mutation" Clin Endocrinol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kambe Fukushi et al.: "An additional carbohydrate chain in the variant thyroxine-binding globulin (TBG asp-96) impairs its secretion" Molecular Endocrinology. 6. 443-449 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yuichi Mori et al.: "Thyroxine-binding globulin (TBG) abnormalities and TBG gene.(in Japanese)" Medicina. 31. 302-305 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hisao Seo et al.: "Inherited thyroxine-binding globulin (TBG) abnormalities.(in Japanese)" Clin Endocrinol. 40. 1221-1227 (1992)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1995-03-27  

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