Impaired spermatogenesis and male fertility defects in CIZ/Nmp4-disrupted mice
Impaired spermatogenesis and male fertility defects in CIZ/Nmp4-disrupted mice
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DOI：
10.1111/j.1356-9597.2004.00746.x
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发表时间：
2004-06-01
期刊：
影响因子：
2.1
通讯作者：
Hirai, H
中科院分区：
文献类型：
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作者：
Nakamoto, T;Shiratsuchi, A;Hirai, H
CIZ（Cas interacting zinc finger protein，Cas锌指蛋白），又称核基质蛋白4（nuclear matrix protein 4，Nmp 4），是一种核质穿梭转录因子，调节胶原蛋白和基质金属蛋白酶的表达。CIZ/Nmp 4最初是通过与p130（Cas）结合而克隆的，p130是一种粘着斑蛋白，最近显示出抑制BMP 2（骨形态发生蛋白2）信号传导。为了探索CIZ/Nmp 4的生理作用，我们通过将β-半乳糖苷酶和新霉素抗性基因插入CIZ/Nmp 4-基因的第二外显子来破坏CIZ/Nmp 4-基因，这被所有测序的替代形式所利用。CIZ（-/-）小鼠出生并生长至成年。虽然它们往往比野生型小鼠小，但除睾丸外，未观察到病理异常。睾丸组织学分析显示CIZ（-/-）小鼠曲细精管内生精细胞变性程度不同，与“生殖细胞发育不全伴局灶性生精”的组织学相似。一些CIZ（-/-）雄性小鼠出现不育。睾丸切片TUNEL法检测CIZ（-/-）小鼠睾丸生精细胞凋亡率增加。CIZ/Nmp 4与Smad 1在睾丸中共定位，表明BMP信号转导失调可能导致这些表型。这些结果表明CIZ/Nmp 4在精子发生的进程和维持中起作用。
CIZ (Cas interacting zinc finger protein), also called Nmp4 (nuclear matrix protein 4), is a nucleocytoplasmic shuttling transcription factor that regulates the expression of collagen and matrix metalloproteinases. CIZ/Nmp4 was originally cloned by its binding to p130(Cas), a focal adhesion protein, and was recently shown to suppress BMP2 (bone mophogenetic protein 2) signalling. To explore the physiological role of CIZ/Nmp4, we disrupted CIZ/Nmp4-gene by inserting beta-galactosidase and neomycin resistance genes into the 2nd 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 apoptosis of spermatogenic cells in the testes of CIZ(-/-) mice. CIZ/Nmp4 was co-localized with Smad1 in the testis, suggesting that a disregulation of BMP signalling could cause these phenotypes. These results suggest that CIZ/Nmp4 plays roles in the progress and the maintenance of spermatogenesis.