Germinal Cell Aplasia in Kif18a Mutant Male Mice Due to Impaired Chromosome Congression and Dysregulated BubR1 and CENP-E

	Germinal Cell Aplasia in Kif18a Mutant Male Mice Due to Impaired Chromosome Congression and Dysregulated BubR1 and CENP-E
	Liu XS 1; Zhao XD 1; Wang XM 3; Yao YX 1,3; Zhang LL 4; Shu RZ 4; Ren WH 2; Huang Y 3; Huang L 1; Gu MM 1
刊名	Genes & cancer
	2010
卷号	1 期号:1 页码:26-39
关键词	BubR1 KIF18A chromosome congression knockout mice testis development
通讯作者	zhugangw@shsmu.edu.cn
英文摘要	Chromosomal instability during cell division frequently causes cell death or malignant transformation. Orderly chromosome congression at the metaphase plate, a paramount process to vertebrate mitosis and meiosis, is controlled by a number of molecular regulators, including kinesins. Kinesin-8 (Kif18A) functions to control mitotic chromosome alignment at the mid-zone by negative regulation of kinetochore oscillation. Here the authors report that disrupting Kif18a function results in complete sterility in male but not in female mice. Histological examination reveals that Kif18a(-/-) testes exhibit severe developmental impairment of seminiferous tubules. Testis atrophy in Kif18a(-/-) mice is caused by perturbation of microtubule dynamics and spindle pole integrity, leading to chromosome congression defects during mitosis and meiosis. Depletion of KIF18A via RNAi causes mitotic arrest accompanied by unaligned chromosomes and increased microtubule nucleating centers in both GC-1 and HeLa cells. Prolonged depletion of KIF18A causes apoptosis due to perturbed microtubule dynamics. Further studies reveal that KIF18A silencing results in degradation of CENP-E and BubR1, which is accompanied by premature sister chromatid separation. KIF18A physically interacts with BubR1 and CENP-E, and this interaction is modulated during mitosis. Combined, the studies indicate that KIF18A is essential for normal chromosome congression during cell division and that the absence of KIF18A function causes severe defects in microtubule dynamics, spindle integrity, and checkpoint activation, leading to germinal cell aplasia in mice.
收录类别	SCI
资助信息	This study was supported in part by US Public Service Awards to WD (CA090658 and CA113349). This work was also partially supported by the grants from National Natural Science Foundation of China (30871420, 30530390), Ministry of Science and Technology of China (2006BAI23B02), and the Science and Technology Commission of Shanghai Municipality (06DZ05907, 07DZ22929) to ZGW, E-Institut
语种	英语
公开日期	2014-07-07
内容类型	期刊论文
源URL	[http://159.226.149.42:8088/handle/152453/7940]
专题	昆明动物研究所_科研共享资源
作者单位	1.Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China 2.Shanghai Research Centre for Model Organisms, Shanghai, China 3.Department of Environmental Medicine & Pharmacology, New York University School of Medicine, Tuxedo, NY, USA 4.Laboratory of Genetic Engineering, Institute of Health Sciences, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences and SJTUSM, Shanghai, China 5.State Key Laboratory of Medical Genomics, Rui-jin Hospital Affiliated with SJTUSM, Shanghai, China 6.Department of Histology and Embryology, Faculty of Basic Medicine, SJTUSM, Shanghai, China
推荐引用方式 GB/T 7714	Liu XS,Zhao XD,Wang XM,et al. Germinal Cell Aplasia in Kif18a Mutant Male Mice Due to Impaired Chromosome Congression and Dysregulated BubR1 and CENP-E[J]. Genes & cancer,2010,1(1):26-39.
APA	Liu XS.,Zhao XD.,Wang XM.,Yao YX.,Zhang LL.,...&Wang ZG[*].(2010).Germinal Cell Aplasia in Kif18a Mutant Male Mice Due to Impaired Chromosome Congression and Dysregulated BubR1 and CENP-E.Genes & cancer,1(1),26-39.
MLA	Liu XS,et al."Germinal Cell Aplasia in Kif18a Mutant Male Mice Due to Impaired Chromosome Congression and Dysregulated BubR1 and CENP-E".Genes & cancer 1.1(2010):26-39.