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Analysisof CIZ disrupted mice

CIZ 破坏小鼠的分析

基本信息

批准号：
14570179
负责人：
HANGAISHI Akira
金额：
$ 2.11万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570179/
关键词：
CIZ knockout mouse apoptosis spermatogenic cell BMP

项目摘要

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.

CIZ(Cas interinteracting zinc finger protein)，又称Nmp4 (nuclear matrix protein 4)，是一种调节胶原蛋白和基质金属蛋白酶表达的核胞质穿梭转录因子。CIZ/Nmp4最初是通过结合p130^<cus>（一种局灶黏附蛋白）克隆出来的，最近被证明可以抑制BMP2（骨形态发生蛋白2）信号传导。为了探索CIZ/Nmp4的生理作用，我们将β -半乳糖苷酶和新霉素耐药基因插入CIZ/Nmp4基因的2^<和>外显子，从而破坏了CIZ/Nmp4基因，这些基因被所有测序的替代形式所利用。CIZ^<-/->小鼠出生并长大成年。虽然它们往往比野生型小鼠小，但除睾丸外未见病理异常。睾丸组织学分析显示，CIZ^<-/->小鼠精管内不同程度的生精细胞变性，类似于局灶性生精的生殖细胞发育不全的组织学。部分CIZ^<-/->雄性小鼠出现不育。睾丸切片TUNEL分析显示，CIZ^<-/->小鼠睾丸生精细胞凋亡发生率增加。在睾丸中，CIZ/Nmp4与Smadl共定位，表明BMP信号的失调可能导致这些表型。这些结果表明，CIZ/Nmp4在精子发生的过程和维持中起着重要作用。