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

1993 Fiscal Year Final Research Report Summary

Analysis of chondrodysplasias using transgenic mouse model.

Research Project

Project/Area Number 03454362
Research Category

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

Allocation TypeSingle-year Grants
Research Field Orthopaedic surgery
Research InstitutionOsaka University

Principal Investigator

KIMURA Tomoatsu  Osaka University Medical School, Department of Orthopaedic Surgery, Assistant Professor, 医学部, 講師 (80167379)

Co-Investigator(Kenkyū-buntansha) ONO Keiro  Osaka University Medical School, Department of Orthopaedic Surgery, Professor an, 医学部, 教授 (70028330)
OCHI Takahiro  Osaka University Medical School, Department of Environmental Medicine, Professor, 医学部, 教授 (80112035)
Project Period (FY) 1991 – 1993
Keywordscartilage / collagen / transgenic mouse / osteoarthritis
Research Abstract

Type IX collagen is a hybrid extracellular matrix component, with the properties of both a proteoglycan and a collagen. It is found in hyaline cartilage, vitreous humor and embryonic cornea, where it is located along the surfaces of type II-containing collagen fibrils. To investigate the functional role of type IX collagen in cartilage, we have introduced an alphal(IX) gene construct expressing a truncated alphal(IX) chain into mice. The construct was designed with an in frame deletion in the central part of alphal(IX) cDNA and tissue specific expression in cartilages and eyes was obtained by using the type II collagen promoter-enhancer. In mouse tissues the transgene was expressed as shortened alphal(IX) chains that were disulfide-bonded with endogenous polypeptides to form collagenous molecules. Light and electron microscopic examination of the offspring of three different founders revealed pathological changes similar to osteoarthritis in the articular cartilage of knee joints. In addition, mice homozygous for the transgene developed mild chondrodysplasia ; i.e., mild dwarfism, anterior tonguing in the vertebral bodies, and ophthalmopathy. The relative ratio of transgene product to the endogenous alphal(IX) chain was approximately one in homozygotes and less than one in heterozygotes. Therefore, the phenotypic severity correlated well with the level of transgene expression. Given these findings, it is possible that mutations in type IX collagen genes may cause certain forms of chondrodysplasia and osteoarthritis in humans.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] K.Nakata,at al.: "Ostcocrothintis associated with unild choondrodysplasiab in transgenic mice expressing α1 (IX) collagen chaius with a central delction" Proc.Natl.Acad.Sci.USA. 90. 2870-2874 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Iwasaki,et al.: "Transforming growth factor-Al stimaletes chondrogenesis and in hibits ostcogenisis in high density culture of peviosteum-devived cells" Eudocrinology. 132. 1603-1608 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Warman,et al.: "Monoclonal antiboies against two epitopes in the human α1 (IX) collagen chain" Matrix. 13. 149-156 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Kimura,et al.: "in “Cell Mechanics and Cellular Engineering"" Springer-Verlag,New York, 564 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Nakata, et al.: "Osteoarthritis associated with mild chondrodysplasia in transgenic mice expressing alphal(IX) collagen chains with a central deletion" Proc.Natl.Acad.Sci.USA. 90. 2870-2874 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Iwasaki, et al.: "Transforming growth factor-beta1 stimulates chondrogenesis and inhibits osteogenesis in high density culture of periouteum-derived cells." Endocrinology. 132. 1603-1608 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Warman, et al.: "Monoclonal antibodies against two epitopes in the human alphal(IX) collagen chain." Matrix. 13. 149-156 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kimura, et al.: Altered chondrocyte gene expression in articular cartilage matrix components and susceptibility to cartilage destruction. in Cell Mechanics and Cellular Engineering (Eds.V.C.Mow, et al.). Springer-Verlag, New York, 445-456

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

URL: 

Published: 1999-03-09  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi