| Project/Area Number |
04671468
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Nagoya University |
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Principal Investigator |
MORI Yuichi Nagoya Uni. School of Medicine Assistant Prof., 医学部, 助手 (70230084)
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| Co-Investigator(Kenkyū-buntansha) |
OKAMOTO Hideki Nagoya Uni. School of Medicine Medical staff, 医学部, 医員
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Thyroxine-binding globulin / Complete deficiency / Partial deficiency / Excess / Frameshift mutation / Gene screening / Intracellular transport / HNF-1 / TBG異常症 / 遺伝子解析 / クローニング / 転写調節 |
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| 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.
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