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| 1 | High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes显示文摘Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening(HTS) data for 3 762 distinct global gene knockout(KO) mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type(WT) cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging,ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass: 23 previously reported genes(Calcr, Cebpb, Crtap, Dcstamp, Dkk1, Duoxa2, Enpp1, Fgf23, Kiss1/Kiss1 r, Kl(Klotho),Lrp5, Mstn, Neo1, Npr2, Ostm1, Postn, Sfrp4, Slc30a5, Slc39a13, Sost, Sumf1, Src, Wnt10b), five novel genes extensively characterized(Cldn18, Fam20 c, Lrrk1, Sgpl1, Wnt16), five novel genes with preliminary characterization(Agpat2, Rassf5, Slc10a7, Slc26a7, Slc30a10) and three novel undisclosed genes coding for potential osteoporosis drug targets. | Robert Brommage Jeff Liu Gwenn M Hansen Laura L Kirkpatrick David G Potter Arthur T Ss Brian Zambrowicz David R Powell Peter Vogel | 2014 | Bone Research2014，2，3： | 7 |
| 2 | 新致病基因在颅缝早闭Crouzon综合征中的初步机制研究显示文摘目的研究Rbp4(Retinol binding protein 4)、Gpc3(Glypican family of growth factor binding protein 3)、C1qtnf3(Collagenous repeat-containing sequence of 26 KDa protein)等新致病基因在颅缝早闭症中的发病机制,为疾病非手术治疗奠定理论基础。方法以Crouzon综合征Fgfr2cC342Y/+小鼠为实验模型,应用MicroCT和组织学染色,研究小鼠颅缝闭合模式;以Fgfr2cC342Y/+模型,RT-qPCR研究Rbp4、Gpc3、C1qtnf3等新致病基因的表达差异,初步探讨其在颅缝闭合过程中的调控作用;以体外培养的Fgfr2cC342Y/+小鼠颅缝细胞为模型,研究基因突变动物细胞增殖与代谢改变。结果获得Fgfr2cC342Y/+小鼠后额缝、冠状缝、人字缝、矢状缝等颅缝闭合模式,随颅骨发育、颅缝闭合,OC(Osteocalcin)、ALP(Alkalinephosphatase)表达增加,目的基因Rbp4、Gpc3、C1qtnf3表达下降,Msx2(Muscle segment homeobox gene 2)表达增加,杂合子与野生型小鼠之间均存在显著统计学差异,与前期人颅缝组织Microarray研究结果一致。Gpc1(Glypican family ofgrowth factor binding protein 1)、FliI(Flightless I)在颅缝闭合中的表达较恒定,野生型与杂合子之间未见明显统计学差异。体外培养Fgfr2cC342Y/+小鼠颅缝细胞,CellTiter96 MTS和Quant-iT Picogreen dsDNA细胞增殖与代谢分析结果显示,Fgfr2功能获得性突变可促进冠状缝细胞的增殖,从而导致成骨增加,颅缝早闭。结论 Fgfr2cC342Y/+模型新致病基因表达趋势与前期人颅缝组织Microarray研究结果一致,Rbp4、Gpc3、C1qtnf3可能在颅缝早闭中具重要调控作用。 | 杨娴娴 Jodie T Hatfield Susan J Hinze 穆雄铮 Peter J Anderson Barry C Powell | 2012 | 组织工程与重建外科杂志2012，8，5： | 3 |
| 3 | Relationship between ratio of pristane to phytane, crude oil composition and geological environment in Australia显示文摘 | POWELL T G MCKIRDY D M | 1973 | Nature1973，243，124： | 1 |
| 4 | Organizational alignment as competitive advantage显示文摘 | Powell T C | 1992 | Strategie Management Journal1992，13，2： | 1 |
| 5 | Influence of implantable cardioverter-defibrillators on longterm prognosis of survivors of out-of-hospital cardiac arrest 显示文摘 | Powell AC Fuchs T Finkelstein DM | 1993 | Circulation1993，88，3： | 1 |
| 6 | A rapid technique for the isolation and purification of adult cardiac muscle cells having respiratory control and a tolerance to calcium 显示文摘 | Powell T Twist V W | 1976 | Biochem Biophys Res Commun1976，72，： | 1 |
| 7 | Phase Velocity Cine Magnetic Resonance Imaging Measurement of Pulsatile Blood Flow in Children and Young Adults:Invitro and Invivo Validation显示文摘 | Powell AJ Maier SE Chung T | 2000 | Pediatr Cardiol2000，21，5： | 1 |
| 8 | Competitive advantage: Logical and philosophical considerations 显示文摘 | Powell T | 2001 | Strategic Man- agement Journal2001，22，9： | 1 |
| 9 | Randomized trial of pulmo?nary valve replacement with and without right ventricular remod?eling surgery显示文摘 | Geva T Gauvreau K Powell AJ | | 0，，11： | 1 |
| 10 | Relationship between ratio of pristine to phytane, crude oil composition and geological environments inAustralia显示文摘 | Powell T Mckirdy D M | 1973 | Nature1973，243，： | 1 |
| 11 | Review: Adiponeetin - the missing link between maternal adiposity, placental transport and fetalgrowth 显示文摘 | Aye IL Powell TL Jansson T | 2013 | Placenta2013，34，： | 1 |
| 12 | Revisiting Managerial Perspectives on Dividend Policy 显示文摘 | Baker H K Powell G E Veit E T | 2002 | Journal of Economics & Finance2002，26，3： | 1 |
| 13 | A double blind, randomized, controlled trial of glutamine supplementation in parenteral nutrition显示文摘 | Powell T J Jamieson C P Bettany G E | 1999 | Gut1999，45，1： | 1 |
| 14 | Comparison of postoperative pain between laser assisted uvulopalatoplasty,uvulopalatopharyngoplasty and radiofrequency volumetric tissue reduction of the palate显示文摘 | Troell T J Powell N B Riley T W | 2000 | Otolaryngol Head Neck Surg2000，122，： | 1 |
| 15 | Reduced drag coefficient for high wind speeds in tropical cyclones显示文摘 | POWELL M D VICKERY P J REINHOLD T A | 2003 | Nature2003，422，： | 1 |
| 16 | Precipitation of sulfide ores and organic matter:Sulfade reactions at Pine Point,Canada显示文摘 | POWELL T G MACQUEEN R W | 1984 | Science1984，224，4644： | 1 |
| 17 | Wind-driven surface transport in stratified closed basins: Direct versus residual circulations显示文摘 | Strub P T Powell T M | 1986 | Journal of Geophysical Research1986，91，7： | 1 |
| 18 | Laparoscopic renal cryotherapy: biology, techniques and outcomes 显示文摘 | POWELL T WHELAN C SCHWARTZ B F | 2005 | Minerva Urol Nefrol2005，57，2： | 1 |
| 19 | Transgenic expression of pear PGIP in tomato limits fungal colonization 显示文摘 | Powell A L T van Kan J ten Have A | 2000 | Molecular Plant-Microbe Interaction2000，13，： | 1 |
| 20 | Multilocular cysts of kidney显示文摘 | Powell T shackman R Johnson HD | 1951 | Br J Urol1951，3，2： | 1 |
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