| Project/Area Number |
14570179
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HANGAISHI Akira The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (20344450)
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| Co-Investigator(Kenkyū-buntansha) |
神田 善伸 東京大学, 医学部附属病院, 助手 (30334379)
黒川 峰夫 東京大学, 医学部附属病院, 講師 (80312320)
CHIBA Shigeru The University of Tokyo, Faculty of Medicine, Associate Professore, 医学部附属病院, 助教授 (60212049)
小川 誠司 東京大学, 医学部附属病院, (常勤形態)客員助教授 (60292900)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | CIZ / knockout mouse / apoptosis / spermatogenic cell / BMP |
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| Research Abstract |
CIZ(Cas interactig zinc finger protein), also called Nmp4 (nuclear matrix protein 4), is a nucleo-cytoplasic shuttling transcription factor that regulates the expression of collagen and matrix metalloproteinases. CIZ/Nmp4 was originally cloned by its binding to p130^<cus>, a focal adhesion protein, and was recently shown to suppress BMP2 (bone mophogenetic protein 2) signaling. To explore the physiological role of CIZ/Nmp4, we disrupted CIZ/Nmp4-gene by inserting beta-galactosidase and neomycin resistance genes into the 2^<nd> exon of CIZ/Nmp4-gene, which is utilized by all the sequenced alternative forms. CIZ^<-/-> mice were born and grew to adulthood. Although they tend to be smaller than wild type mice, no pathological abnormality was observed except in the testis. Histological analysis of the testes revealed variable degrees of spermatogenic cell degeneration within the seminiferous tubules of CIZ^<-/-> mice, resembling the histology of the Germinal-cell aplasia with focal spermatogenesis. Some of the CIZ^<-/-> male mice developed infertility. TUNEL assay on testis sections revealed an increased occurrence of poptosis of spermatogenic cells in the testes of CIZ^<-/-> mice. CIZ/Nmp4 was colocalized with Smadl in the testis, suggesting that a disregulation of BMP signaling could cause these phenotypes. These results suggest that CIZ/Nmp4 plays roles in the progress and the maintenance of spermatogenesis.
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