Osteoarthritis associated with mild chondrodysplasia in transgenic mice expressing alpha 1(IX) collagen chains with a central deletion.
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- K Nakata
- Department of Orthopaedic Surgery, Osaka University Medical School, Japan.
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- K Ono
- Department of Orthopaedic Surgery, Osaka University Medical School, Japan.
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- J Miyazaki
- Department of Orthopaedic Surgery, Osaka University Medical School, Japan.
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- B R Olsen
- Department of Orthopaedic Surgery, Osaka University Medical School, Japan.
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- Y Muragaki
- Department of Orthopaedic Surgery, Osaka University Medical School, Japan.
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- E Adachi
- Department of Orthopaedic Surgery, Osaka University Medical School, Japan.
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- K Yamamura
- Department of Orthopaedic Surgery, Osaka University Medical School, Japan.
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- T Kimura
- Department of Orthopaedic Surgery, Osaka University Medical School, Japan.
抄録
<jats:p>Type IX collagen, containing molecules of the three distinct polypeptides alpha 1(IX), alpha 2(IX), and alpha 3(IX), is an interesting hybrid extracellular matrix component in cartilage and eye tissues, with the properties of both a proteoglycan and a collagen. The alpha 1 (IX) chain has two forms, as a result of the tissue-specific utilization of two alternative promoters; the alpha 2(IX) chain carries a covalently attached glycosaminoglycan side chain. We have introduced a gene construct controlled by a tissue-specific promoter/enhancer and expressing a truncated alpha 1(IX) chain into mice. Examination of the offspring of two 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 alpha 1(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. These findings suggest that mutations in type IX collagen genes may cause certain forms of osteoarthritis and chondrodysplasia in humans.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 90 (7), 2870-2874, 1993-04
Proceedings of the National Academy of Sciences
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詳細情報 詳細情報について
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- CRID
- 1363388844699524608
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- NII論文ID
- 80007005819
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- ISSN
- 10916490
- 00278424
- http://id.crossref.org/issn/00278424
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