Gene knockout of Zmym3 in mice arrests spermatogenesis at meiotic metaphase with defects in spindle assembly checkpoint

被引：31

作者：

Hu, Xiangjing ^{[1
,2
]}

Shen, Bin ^{[3
]}

Liao, Shangying ^{[1
]}

Ning, Yan ^{[1
,2
]}

Ma, Longfei ^{[1
,2
]}

Chen, Jian ^{[1
,3
]}

Lin, Xiwen ^{[1
]}

Zhang, Daoqin ^{[1
,2
]}

Li, Zhen ^{[1
,2
]}

Zheng, Chunwei ^{[1
,2
]}

Feng, Yanmin ^{[1
,3
]}

Huang, Xingxu ^{[4
]}

Han, Chunsheng ^{[1
]}

机构：

[1] Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, 1-5 Bei Chen West Rd, Beijing 100101, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[3] Nanjing Med Univ, Dept Histol & Embryol, State Key Lab Reprod Med, Nanjing 210029, Jiangsu, Peoples R China

[4] Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China

来源：

CELL DEATH & DISEASE | 2017年 / 8卷

基金：

中国国家自然科学基金;

关键词：

LINKED MENTAL-RETARDATION; SPERMATOGONIAL STEM-CELLS; MALE GERM-CELLS; RETINOIC ACID; MEIOSIS; PROGRESSION; LSD1; EXPRESSION; GENERATION; CHROMATIN;

D O I：

10.1038/cddis.2017.228

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：e2910 / e2910

页数：11

共 31 条

[1] Steroidogenic organ development and homeostasis: A WT1-centric view [J].