Gene knockout of Zmym3 in mice arrests spermatogenesis at meiotic metaphase with defects in spindle assembly checkpoint.
Gene knockout of Zmym3 in mice arrests spermatogenesis at meiotic metaphase with defects in spindle assembly checkpoint.
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小鼠 Zmym3 基因敲除使精子发生停滞在减数分裂中期，纺锤体组装检查点存在缺陷
DOI：
10.1038/cddis.2017.228
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发表时间：
2017-06-29
影响因子：
9
通讯作者：
Han C
中科院分区：
文献类型：
--
作者：
Hu X;Shen B;Liao S;Ning Y;Ma L;Chen J;Lin X;Zhang D;Li Z;Zheng C;Feng Y;Huang X;Han C
ZMYM 3是MYM型锌指蛋白家族的成员，也是含LSD 1的转录抑制因子复合物的组成部分，主要在小鼠脑和睾丸中表达。在这里，我们表明，ZMYM 3在小鼠睾丸中的体细胞和生殖细胞，直到粗线期精母细胞表达。使用CRISPR-Cas9系统在小鼠中敲除（KO）Zmym 3导致成年雄性不育。KO小鼠的精子发生在第一次减数分裂（MI）的中期被阻止。ZMYM 3与精原干细胞中的LSD 1共免疫沉淀，但其KO不改变LSD 1或H3 K4 me 1/2或H3 K9 me 2的水平。然而，Zmym 3 KO导致凋亡生殖细胞和对BUB 3呈阳性的MI精母细胞的数量增加，BUB 3是纺锤体组装检查点中的关键参与者。Zmym 3 KO还导致精原细胞减数分裂基因的表达上调。这些结果表明，ZMYM 3在小鼠精子发生的中期到后期的转换中具有重要作用，通过调节不同家族的基因的表达。
ZMYM3, a member of the MYM-type zinc finger protein family and a component of a LSD1-containing transcription repressor complex, is predominantly expressed in the mouse brain and testis. Here, we show that ZMYM3 in the mouse testis is expressed in somatic cells and germ cells until pachytene spermatocytes. Knockout (KO) of Zmym3 in mice using the CRISPR-Cas9 system resulted in adult male infertility. Spermatogenesis of the KO mice was arrested at the metaphase of the first meiotic division (MI). ZMYM3 co-immunoprecipitated with LSD1 in spermatogonial stem cells, but its KO did not change the levels of LSD1 or H3K4me1/2 or H3K9me2. However, Zmym3 KO resulted in elevated numbers of apoptotic germ cells and of MI spermatocytes that are positive for BUB3, which is a key player in spindle assembly checkpoint. Zmym3 KO also resulted in up-regulated expression of meiotic genes in spermatogonia. These results show that ZMYM3 has an essential role in metaphase to anaphase transition during mouse spermatogenesis by regulating the expression of diverse families of genes.
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影响因子：
3.8
作者：
Maiques-Diaz A;Somervaille TC
通讯作者：
Somervaille TC
影响因子：
4.1
作者：
Bandiera, Roberto;Sacco, Sonia;Schedl, Andreas
通讯作者：
Schedl, Andreas
影响因子：
4
作者：
Wang, Si;Wang, Xiuxia;Han, Chunsheng
通讯作者：
Han, Chunsheng
MicroRNA-202 通过抑制细胞周期调节因子和 RNA 结合蛋白来维持精原干细胞
影响因子：
14.9
作者：
Chen J;Cai T;Zheng C;Lin X;Wang G;Liao S;Wang X;Gan H;Zhang D;Hu X;Wang S;Li Z;Feng Y;Yang F;Han C
通讯作者：
Han C
影响因子：
3.7
作者：
Gocke CB;Yu H
通讯作者：
Yu H