PLoS Genet：基因敲除研究揭示大量基因影响骨骼

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澳大利亚和英国研究人员发现许多基因可能影响骨骼强度，而且这些基因可能在我们的身体内21000个基因当中大约占2000个。在一项新研究中，英国维尔康姆基金会桑格研究所(Wellcome Trust Sanger Institute)参与一项全球行动：敲除小鼠基因组中每个基因，而且是每只小鼠只能敲除一个基因。在100只基因敲除小鼠中，科学家们鉴定出9个基因似乎削弱或加强骨骼。

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来自澳大利亚悉尼市加文医学研究所(Garvan Institute of Medical Research)的教授 Peter Croucher与来自英国伦敦帝国理工学院的教授Graham Williams和博士Duncan Bassett以及来自维尔康姆基金会桑格研究所的同事们合作开展研究，利用显微CT(micro-CT)、数字X射线显微放射照相法(digital x-ray microradiography)，同时结合统计学方法和承载实验(load bearing experiment)，来测量首批100个基因中的每个是否影响骨骼。他们的研究结果在线发表在<em>PLoS Genetics</em>期刊上。研究人员利用这种方法成功地鉴定出9个之前未曾描述过的基因，它们当中的每个基因似乎在调节骨骼中发挥着重要作用。

在当前，研究人员正在试图理解这9个基因的潜在作用。这些研究结果提示着，如果能够阻断它们中的一些，那么这可能会导致骨质增加和更强的骨骼强度。

本文编译自<a href="http://medicalxpress.com/news/2012-08-knockout-reveals-large-genes-affect.html" target="_blank">Knockout finding reveals large number of genes that affect our bones</a>
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<a title="" href="http://dx.doi.org/10.1371/journal.pgen.1002858" target="_blank">doi: 10.1371/journal.pgen.1002858</a>
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<br/><strong>Rapid-Throughput Skeletal Phenotyping of 100 Knockout Mice Identifies 9 New Genes That Determine Bone Strength</strong><br/>


J. H. Duncan Bassett1#, Apostolos Gogakos1, Jacqueline K. White2, Holly Evans3, Richard M. Jacques4, Anne H. van der Spek1, Sanger Mouse Genetics Project, Ramiro Ramirez-Solis2, Edward Ryder2, David Sunter2, Alan Boyde5, Michael J. Campbell4, Peter I. Croucher3,6#*, Graham R. Williams

Osteoporosis is a common polygenic disease and global healthcare priority but its genetic basis remains largely unknown. We report a high-throughput multi-parameter phenotype screen to identify functionally significant skeletal phenotypes in mice generated by the Wellcome Trust Sanger Institute Mouse Genetics Project and discover novel genes that may be involved in the pathogenesis of osteoporosis. The integrated use of primary phenotype data with quantitative x-ray microradiography, micro-computed tomography, statistical approaches and biomechanical testing in 100 unselected knockout mouse strains identified nine new genetic determinants of bone mass and strength. These nine new genes include five whose deletion results in low bone mass and four whose deletion results in high bone mass. None of the nine genes have been implicated previously in skeletal disorders and detailed analysis of the biomechanical consequences of their deletion revealed a novel functional classification of bone structure and strength. The organ-specific and disease-focused strategy described in this study can be applied to any biological system or tractable polygenic disease, thus providing a general basis to define gene function in a system-specific manner. Application of the approach to diseases affecting other physiological systems will help to realize the full potential of the International Mouse Phenotyping Consortium.

<br/>来源：生物谷

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