Gene Mutations and Genomic Rearrangements in the Mouse as a Result of Transposon Mobilization from Chromosomal Concatemers 英文参考文献.docVIP

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Gene Mutations and Genomic Rearrangements in the Mouse as a Result of Transposon Mobilization from Chromosomal Concatemers 英文参考文献.doc

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Gene Mutations and Genomic Rearrangements in the Mouse as a Result of Transposon Mobilization from Chromosomal Concatemers 英文参考文献

GeneMutationsandGenomicRearrangements intheMouseasaResultofTransposon MobilizationfromChromosomalConcatemers Aron M.Geurts1,2,Lara S.Collier2,3,Jennifer L.Geurts2,3,Leann L.Oseth4,Matthew L.Bell5,David Mu6,Robert Lucito6, Susan A.Godbout1,Laura E.Green2,Scott W. Lowe7,Betsy A.Hirsch3,4,8,Leslie A.Leinwand9, David A.Largaespada1,2,3* 1DepartmentofGenetics,CellBiology,andDevelopment,UniversityofMinnesotaTwinCities,Minneapolis,Minnesota,UnitedStatesofAmerica,2TheArnoldandMabel BeckmanCenterforTransposonResearch,UniversityofMinnesotaTwinCities,Minneapolis,Minnesota,UnitedStatesofAmerica,3CancerCenter,UniversityofMinnesota TwinCities,Minneapolis,Minnesota,UnitedStatesofAmerica,4InstituteofHumanGenetics,UniversityofMinnesotaTwinCities,Minneapolis,Minnesota,UnitedStatesof America, 5 Department of Integrative Physiology, University of Colorado, Boulder, Colorado, United States of America, 6 Genome Research Center, Cold Spring Harbor Laboratory,ColdSpringHarbor,NewYork,UnitedStatesofAmerica,7ColdSpringHarborLaboratory,ColdSpringHarbor,NewYork,UnitedStatesofAmerica,8Laboratory MedicineandPathology,UniversityofMinnesotaTwinCities,Minneapolis,Minnesota,UnitedStatesofAmerica,9DepartmentofMolecular,Cellular,andDevelopmental Biology,UniversityofColorado,Boulder,Colorado,UnitedStatesofAmerica Previous studies of the Sleeping Beauty (SB) transposon system, asan insertional mutagen in the germline of mice, haveusedreversegeneticapproaches.Thesestudieshaveledtoitsproposeduseforregionalsaturationmutagenesis bytakingaforward-geneticapproach.Thus,weusedtheSBsystemtomutatearegionofmouseChromosome11ina forward-geneticscreenforrecessivelethalandviablephenotypes.Thisworkrepresentsthefirstreporteduseofan insertional mutagen in a phenotype-driven approach. The phenotype-driven approach was successful in both recovering visible and behavioral mutants, including dominant limb and recessive behavioral phenotypes, and allowing for the rapid identification of candidate gene disruptions. I