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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 | S.T.O.N.E. Nephrolithometry: Novel Surgical Classification System for Kidney Calculi显示文摘 | Zhamshid Okhunov Justin I. Friedlander Arvin K. George Brian D. Duty Daniel M. Moreira Arun K. Srinivasan Joel Hillelsohn Arthur D. Smith Zeph Okeke | 2013 | Urology2013，，6： | 2 |
| 3 | Tumor Necrosis Factor Receptors 1 and 2 Differentially Regulate Survival, Cardiac Dysfunction, and Remodeling in Transgenic Mice With Tumor Necrosis Factor-α–Induced Cardiomyopathy显示文摘 | Yoshihiro Higuchi Charles F. McTiernan Carole B. Frye Brian S. McGowan Tung O. Chan Arthur M. Feldman | 2004 | Circulation: Journal of the American Heart Association2004，，15： | 2 |
| 4 | The Tryptophan Hydroxylase Inhibitor LX1031 Shows Clinical Benefit in Patients With Nonconstipating Irritable Bowel Syndrome显示文摘 | Philip M. Brown Douglas A. Drossman Alastair J.J. Wood Gary A. Cline Kenny S. Frazier Jessica I. Jackson Johanna Bronner Joel Freiman Brian Zambrowicz Arthur Sands Michael D. Gershon | 2011 | Gastroenterology2011，，2： | 2 |
| 5 | NOTUM inhibition increases endocortical bone formation and bone strength显示文摘The disability,mortality and costs caused by non-vertebral osteoporotic fractures are enormous.Existing osteoporosis therapies are highly effective at reducing vertebral but not non-vertebral fractures.Cortical bone is a major determinant of non-vertebral bone strength.To identify novel osteoporosis drug targets,we phenotyped cortical bone of 3 366 viable mouse strains with global knockouts of druggable genes.Cortical bone thickness was substantially elevated in Notum?/?mice.NOTUM is a secreted WNT lipase and we observed high NOTUM expression in cortical bone and osteoblasts but not osteoclasts.Three orally active small molecules and a neutralizing antibody inhibiting NOTUM lipase activity were developed.They increased cortical bone thickness and strength at multiple skeletal sites in both gonadal intact and ovariectomized rodents by stimulating endocortical bone formation.Thus,inhibition of NOTUM activity is a potential novel anabolic therapy for strengthening cortical bone and preventing non-vertebral fractures. | Robert Brommage Jeff Liu Peter Voge Faika Mseeh Andrea Y.Thompson David G.Potter Melanie K.Shadoan Gwenn M.Hansen Sabrina Jeter-Jones Jie Cui Dawn Bright Jennifer P.Bardenhagen Deon D.Doree Sofia Moverare-Skrtic Karin H.Nilsson Petra Henning Ulf H.Lerner Claes Ohlsson Arthur T.Sands James E.Tarver David R.Powell Brian Zambrowicz Qingyun Liu | 2019 | Bone Research2019，7，1： | 2 |
| 6 | The path forward for bio- fuels and biomaterials显示文摘 | Arthur J R Charlotte K W Brian H D | 2006 | Science2006，311，5760： | 1 |
| 7 | The Path Forward for Biofuels and Biomaterials 显示文摘 | Arthur J Ragauskas Charlotte K Williams Brian H Davison | 2006 | Science2006，311，： | 1 |
| 8 | Complexity and Economy显示文摘 | Brian Arthur | | 0，，02： | 1 |
| 9 | Considerations for development of Marcellus Shale gas 显示文摘 | Daniel Arthur J Brian Bohm Mark Layne | 2009 | World Oil2009，，6： | 1 |
| 10 | The path forward for biofuels and biomaterals显示文摘 | Arthur J Ragauskas Charlotte K Williams Brian H Davison | 2006 | Science2006，311，27： | 1 |
| 11 | The pathway forward for biofuels and biomaterials 显示文摘 | ARTHUR J R CHARLOTrE K W BRIAN H D | 2006 | Sci2006，311，： | 1 |
| 12 | Complexity in Economic and Financial Markets显示文摘 | Brian Arthur | 1995 | Complexity1995，1，1： | 1 |
| 13 | Increasing Returns and the New World of Business显示文摘 | Arthur Brian W | 1996 | Harvard Business Review1996，，： | 1 |
| 14 | Competing technologies,increasing returns,and lock-in by historical events显示文摘 | Arthur Brian | 1989 | Economic Journal1989，99，： | 1 |
| 15 | The path forward for biofuels and biomaterials显示文摘 | Arthur J Ragauskas Charlotte KWilliams Brian H Davison | 2006 | Science2006，311，： | 1 |
| 16 | The path forward for biofuelsand biomaterials显示文摘 | Arthur J Ragauskas Charlotte K Williams Brian H Davison | 2006 | Science2006，311，： | 1 |
| 17 | Silicon Valley Locational Cluster:When Do Increasing Returns Imply Monoploy显示文摘 | Brian | 1990 | Mathematical Social Sciences1990，，3： | 1 |
| 18 | Spontaneous Control of HCV Is Associated With Expression of HLA-B*57 and Preservation of Targeted Epitopes显示文摘 | Arthur Y. Kim Thomas Kuntzen Joerg Timm Brian E. Nolan Melanie A. Baca Laura L. Reyor Andrew C. Berical Andrea J. Feller Kristin L. Johnson Julian Schulze Zur Wiesch Gregory K. Robbins Raymond T. Chung Bruce D. Walker Mary Carrington Todd M. Allen Georg M | 2011 | Gastroenterology2011，，2： | 1 |
| 19 | The path forwards for biofuels and biomaterials显示文摘 | Arthur J R Charltte K W Brian H D | 2006 | Science2006，311，27： | 1 |
| 20 | Competing Technologies, Increasing Returns, and Lock-in Historical events显示文摘 | ARTHUR W BRIAN | 1989 | Economic Journal1989，99，394： | 1 |
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