| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
ADAMTS-1 is an ADAM family protein with thrombospondin(ISP) type I motifs. By analyzing ADAMTS-1 gene knockout mice, we have shown that ADAMTS-1 is a multifunctional metalloproteinase that is essential for the structure and function of the ureteropelvic junction and adrenal glands as well as of the female genital organs. In addition, we previously demonstrated that ADAMTS-1 is able to cleave a major cartilage proteoglycan, aggrecan. Since the ADAMTS-1 cleavage sites of aggrecan correspond to the in vivo cleavage sites of aggrecan, which have been identified from aggrecan fragments in the synovial fluid of arthritis patients, it is possible that ADAMTS-1 may be involved in the degradation of cartilage tissue during arthritis through the degradation of aggrecan in vivo. The purpose of this study is to clarify the role of ADAMTS-1 on the degradation of cartilage in a collagen-induced arthritis model. ADAMTS-1(-/-) mice were backcrossed to DBA1 mice for ten generations and we are in the process of breeding knockout mice, needed for this experiment. In the meantime, examination of the ovarian function of ADAMTS-1(-/-) female mice has been preceding because it was found that fertilization was severely impaired in ADAMTS-1(-/-) females. When 3-week-old female mice were treated with PMSG and hCG, ADAMTS-1(-/-) females ovulated very few oocytes, approximately one-eighth the number ovulated by ADAMTS-1(+/-), indicating that the overroll ovarian function of ADAMTS-1(-/-) female mice is impaired. This finding suggests that ADAMTS-1 is essential for the ovarian function.
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