Walker Michael P, Tian Liping, Matera A Gregory
Department of Genetics, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
PLoS One. 2009 Jul 9;4(7):e6171. doi: 10.1371/journal.pone.0006171.
Coilin is the signature protein of the Cajal body, a conserved nuclear organelle involved in multiple aspects of small ribonucleoprotein (RNP) biogenesis. Coilin is required for Cajal body homeostasis in both plants and animals. Mice lacking coilin are viable when the mutation is crossed to an outbred strain but only partially viable when crossed to inbred lines.
METHODOLOGY/PRINCIPAL FINDINGS: In order to clarify this issue, we backcrossed the coilin deletion onto the C57BL6/J background for ten generations and then investigated the consequences of coilin removal on overall viability and reproductive success. We conclude that semi-lethal phenotype observed in mixed-background crosses is due to loss of the Coilin gene (or a very tightly-linked locus). Interestingly, coilin knockout embryos die relatively late in gestation, between E13.5 and birth. We show that the maternal contribution of coilin is not important for organismal viability. Importantly, coilin knockout mice display significant fertility and fecundity defects. Mutant males that escape the embryonic lethality display reduced testis size, however, both males and females contribute to the observed reduction in reproductive fitness.
CONCLUSIONS/SIGNIFICANCE: The evolutionary conservation of coilin from plants to animals suggests that the protein plays an important role, perhaps coordinating the activities of various RNA-processing machineries. Our observations are consistent with the idea that coilin functions to ensure robust organismal development, especially during periods of rapid growth.
卷曲螺旋蛋白是卡哈尔体的标志性蛋白,卡哈尔体是一种保守的核细胞器,参与小核糖核蛋白(RNP)生物合成的多个方面。卷曲螺旋蛋白在植物和动物的卡哈尔体稳态中都是必需的。当卷曲螺旋蛋白缺失的突变与远交系杂交时,小鼠能够存活,但与近交系杂交时仅部分存活。
方法/主要发现:为了阐明这个问题,我们将卷曲螺旋蛋白缺失基因回交到C57BL6/J背景上十代,然后研究去除卷曲螺旋蛋白对整体活力和繁殖成功率的影响。我们得出结论,在混合背景杂交中观察到的半致死表型是由于卷曲螺旋蛋白基因(或一个紧密连锁的位点)的缺失。有趣的是,卷曲螺旋蛋白基因敲除胚胎在妊娠后期相对较晚死亡,即在E13.5和出生之间。我们表明,卷曲螺旋蛋白的母体贡献对生物体的活力并不重要。重要的是,卷曲螺旋蛋白基因敲除小鼠表现出明显的生育力和繁殖力缺陷。逃脱胚胎致死的突变雄性小鼠睾丸尺寸减小,然而,雄性和雌性都导致了观察到的生殖适应性下降。
结论/意义:从植物到动物,卷曲螺旋蛋白的进化保守性表明该蛋白起着重要作用,可能是协调各种RNA加工机制的活动。我们的观察结果与卷曲螺旋蛋白的功能是确保强大的生物体发育,特别是在快速生长时期的观点一致。