Hudson D F, Fowler K J, Earle E, Saffery R, Kalitsis P, Trowell H, Hill J, Wreford N G, de Kretser D M, Cancilla M R, Howman E, Hii L, Cutts S M, Irvine D V, Choo K H
The Murdoch Institute for Research into Birth Defects, Royal Children's Hospital, Parkville 3052, Australia.
J Cell Biol. 1998 Apr 20;141(2):309-19. doi: 10.1083/jcb.141.2.309.
CENP-B is a constitutive centromere DNA-binding protein that is conserved in a number of mammalian species and in yeast. Despite this conservation, earlier cytological and indirect experimental studies have provided conflicting evidence concerning the role of this protein in mitosis. The requirement of this protein in meiosis has also not previously been described. To resolve these uncertainties, we used targeted disruption of the Cenpb gene in mouse to study the functional significance of this protein in mitosis and meiosis. Male and female Cenpb null mice have normal body weights at birth and at weaning, but these subsequently lag behind those of the heterozygous and wild-type animals. The weight and sperm content of the testes of Cenpb null mice are also significantly decreased. Otherwise, the animals appear developmentally and reproductively normal. Cytogenetic fluorescence-activated cell sorting and histological analyses of somatic and germline tissues revealed no abnormality. These results indicate that Cenpb is not essential for mitosis or meiosis, although the observed weight reduction raises the possibility that Cenpb deficiency may subtly affect some aspects of centromere assembly and function, and result in reduced rate of cell cycle progression, efficiency of microtubule capture, and/or chromosome movement. A model for a functional redundancy of this protein is presented.
着丝粒蛋白B（CENP-B）是一种组成型着丝粒DNA结合蛋白，在许多哺乳动物物种和酵母中都保守存在。尽管存在这种保守性，但早期的细胞学和间接实验研究对于该蛋白在有丝分裂中的作用提供了相互矛盾的证据。此前也未曾描述过该蛋白在减数分裂中的需求。为了解决这些不确定性，我们利用小鼠中Cenpb基因的靶向破坏来研究该蛋白在有丝分裂和减数分裂中的功能意义。雄性和雌性Cenpb基因敲除小鼠在出生和断奶时体重正常，但随后体重落后于杂合子和野生型动物。Cenpb基因敲除小鼠睾丸的重量和精子含量也显著降低。除此之外，这些动物在发育和生殖方面看起来正常。细胞遗传学荧光激活细胞分选以及体细胞和生殖细胞组织的组织学分析均未发现异常。这些结果表明，Cenpb对于有丝分裂或减数分裂并非必不可少，尽管观察到的体重减轻增加了一种可能性，即Cenpb缺乏可能会微妙地影响着丝粒组装和功能的某些方面，并导致细胞周期进程速率降低、微管捕获效率降低和/或染色体移动受影响。本文提出了该蛋白功能冗余的模型。
