上海 2012年8月9日 訊 /生物谷BIOON/ --澳大利亞和英國研究人員發(fā)現(xiàn)許多基因可能影響骨骼強(qiáng)度,，而且這些基因可能在我們的身體內(nèi)21000個基因當(dāng)中大約占2000個。在一項新研究中,，英國維爾康姆基金會桑格研究所(Wellcome Trust Sanger Institute)參與一項全球行動：敲除小鼠基因組中每個基因,，而且是每只小鼠只能敲除一個基因,。在100只基因敲除小鼠中,，科學(xué)家們鑒定出9個基因似乎削弱或加強(qiáng)骨骼,。
來自澳大利亞悉尼市加文醫(yī)學(xué)研究所(Garvan Institute of Medical Research)的教授 Peter Croucher與來自英國倫敦帝國理工學(xué)院的教授Graham Williams和博士Duncan Bassett以及來自維爾康姆基金會桑格研究所的同事們合作開展研究，利用顯微CT(micro-CT),、數(shù)字X射線顯微放射照相法(digital x-ray microradiography)，同時結(jié)合統(tǒng)計學(xué)方法和承載實驗(load bearing experiment),，來測量首批100個基因中的每個是否影響骨骼,。他們的研究結(jié)果在線發(fā)表在PLoS Genetics期刊上。研究人員利用這種方法成功地鑒定出9個之前未曾描述過的基因,，它們當(dāng)中的每個基因似乎在調(diào)節(jié)骨骼中發(fā)揮著重要作用,。
在當(dāng)前，研究人員正在試圖理解這9個基因的潛在作用,。這些研究結(jié)果提示著,，如果能夠阻斷它們中的一些，那么這可能會導(dǎo)致骨質(zhì)增加和更強(qiáng)的骨骼強(qiáng)度,。(生物谷：Bioon.com)
本文編譯自Knockout finding reveals large number of genes that affect our bones
doi: 10.1371/journal.pgen.1002858
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PMID:
Rapid-Throughput Skeletal Phenotyping of 100 Knockout Mice Identifies 9 New Genes That Determine Bone Strength
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.
