• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1992 Fiscal Year Final Research Report Summary

Pathophysiological investigation on cerebrotendinous xanthomatosis

Research Project

Project/Area Number 02044044
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionThe University of Tokyo

Principal Investigator

SEYAMA Yousuke  The University of Tokyo, Faculty of Medicine, Professor, 医学部(医), 教授 (90010082)

Co-Investigator(Kenkyū-buntansha) SALEN Gerald  University of Medicine and Dentistry of New Jersey, Professor, 医学部, 教授
SHEFER Sarah  University of Medicine and Dentistry of New Jersey, Professor, 医学部, 教授
BJOERKHEM IN  カロリンスカ研究所, 教授
笠間 健嗣  東京医科歯科大学, 医学部, 助手 (80124668)
KUBOTA Shunichiro  The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部(医), 助教授
HOSHITA Takahiko  Hiroshima University School of Medicine, Professor, 医学部, 教授 (60033966)
YONEMOTO Kyozo  Jikei University School of Medicine,Professor, 医学部, 教授 (80056572)
BIOERKHEM Ingemar  Karolinska Institutet, Huddinge University Hospital, Professor
KASAMA Takeshi  Tokyo Medical and Dental University, Faculty of Medicine, Associate
Project Period (FY) 1990 – 1992
Keywordscerebrotendinous xanthomatosis / CTX / cholestanol / genetic diagnosis / PCR / restriction enzyme / experimental model animal / gallstone formation
Research Abstract

Cerebrotendinous xanthomatosis is a metabolic disease, characterized by neurologic dysfunction, tendon xanthomas and juvenile cataracts. CTX patients have an impaired capacity to convert cholesterol to bile acids, due to a defect of hepatic enzyme, which catalyzes the oxidation of side chains of sterol intermediates. The first case in Japan was reported by Shibasaki in 1969.
We intended first to clarify the genetic mutations in CTX patients, and secondly to establish an experimental model animal of this disease.
1. Genetic abnormalities in CTX patients : In collaboration with Ingemar Bjoerkhem, we (Seyama, Yonemoto, Hoshita and Kubota) analyzed the nucleotide sequence of cDNA encoding the sterol 27-hydroxylase. Direct sequencing of RT-PCR products revealed a mutation at the heme-ligand binding site in five CTX patients. Arginine at the 441 position was replaced by glutamine or tryptophan, and one base deletion was also found in one patient at the position encoding 445th amino acid. In pa … More tients with replacement of arginine by glutamine, a new restriction site with "Stu I" appeared. In patients with a replacement of arginine by tryptophan, "Hpa II" site disappeared. These findings suggest a possibility of genetic diagnosis using RFLP.
2. Establishment of experimental model animal of CTX : In collaboration with Salen and Shefer, we (Seyama and Kasama) established an experimental model animal by feeding cholestanol diet. After feeding 1% cholestanol in the diet, gallstones developed in 20 % of the mice and were associated with gallbladder mucosal inflammation and serosal vessel wall thickening. Hepatic HMG-CoA reductase activity rose by 51 % In contrast cholesterol 7a-hydroxylase activity was severely depressed. Discontinuing cholestanol from the diet for 1 month, reduced the elevated serum and liver cholestanol concentrations, and restored hepatic HMG-CoA reductase and cholesterol 7a-hydroxylase to normal. The combination of increased cholesterol synthesis with decreased bile acid formation promotes gallstone formation in cholestanol fed mice. Less

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Kim,K-S,Kano,K,Shefer,S.,Salen,G. and Seyama,Y.: "Gellstone formation in cholestanol-fed mice." Journal of Biochemistry. 113. 420-424 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kim,K-S,KANO,K.,KASAMA,T.ISHII,Y.,YAMASHITA,H. and SEYAMA,Y.: "Effects of cholestanol feeding on corneal dystrophy in mice." Biochim.Biophys.Acta. 1085. 343-349 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Bynu,D-S,KASAMA,T.,SHIMIZU,T.,YORIFOJI,H. and SEYAMA,Y.: "Effects of cholestnol feeding sterol concentrations in the serum,liver and cerebellum of mice." Journal of Biochemisrty. 103. 375-379 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] OGAWA,Y.and YONEMOTO,K.: "Activty single human motor units an ipsilateral leg as the contralateal leg exetrs force." Japanese J.of Physical.41. 248 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] UNE,M.,IZUMI,N.,IMANAKA,T.and HOSHITA,T.: "Formation of cholic acid from 3α,7α,12α-trihydroxy-5β-cholestanoic acid in human skin fibroblasts." Journal of Biochemistry. 112. 576-577 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kim, K-S., Kano, K., Shefer, S., Salen, G. and Seyama, Y.: "Gallstone formation in cholestanol-fed mice." Journal of Biochemistry. 113. 420-424 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kim, K-S., Kano, K., Kasama, T., Ishii, Y., Yamashita, H. and Seyama, Y.: "Effects of cholestanol feeding on corneal dystrophy in mice." Biochim. Biophys. Acta. 1085. 343-349 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Byun-D-S., Kasama, T., Shimizu, T., Yorifuji, H. and Seyama, Y.: "Effects of cholestanol feeding on sterol concentrations in the serum, liver and cerebellum of mice." Journal of Biochemistry. 103. 375-379 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ogawa, y. and Yonemoto, K.: "Activity of single human motor units in an ipsilateral leg as the contralateral leg exerts force." Japanese Journal of Physical.41. 248 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Une, M., Izumi, N., Imanaka, Imanaka, T. and Hoshita, T.: "Formation of cholic acid from 3alpha, 7alpha, 12alpha-trihydroxy-5bata-cholestanoic acid in'human skin fibroblasts." Journal of Biochemistry. 112. 576-577 (1992)

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

URL: 

Published: 1994-03-24  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi