{"id":"https://openalex.org/W2531817643","doi":"https://doi.org/10.1182/blood.v120.21.493.493","title":"A Sensitized Whole Genome ENU Mutagenesis Screen Identifies an Arp2 Missense Mutation As a Novel Suppressor of Lethal Thrombosis in the Factor V Leiden Mouse","display_name":"A Sensitized Whole Genome ENU Mutagenesis Screen Identifies an Arp2 Missense Mutation As a Novel Suppressor of Lethal Thrombosis in the Factor V Leiden Mouse","publication_year":2012,"publication_date":"2012-11-16","ids":{"openalex":"https://openalex.org/W2531817643","doi":"https://doi.org/10.1182/blood.v120.21.493.493","mag":"2531817643"},"language":"en","primary_location":{"id":"doi:10.1182/blood.v120.21.493.493","doi":"https://doi.org/10.1182/blood.v120.21.493.493","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v120.21.493.493","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5088882561","display_name":"Randal Joseph Westrick","orcid":"https://orcid.org/0000-0001-8775-8460","observed_orcids":["https://orcid.org/0000-0001-8775-8460"]},"institutions":[{"id":"https://openalex.org/I27837315","display_name":"University of Michigan","ror":"https://ror.org/00jmfr291","country_code":"US","type":"education","lineage":["https://openalex.org/I27837315"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Randal Joseph Westrick","raw_affiliation_strings":["Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA,","institution_ids":["https://openalex.org/I27837315"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5101056654","display_name":"Guojing Zhu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I27837315","display_name":"University of Michigan","ror":"https://ror.org/00jmfr291","country_code":"US","type":"education","lineage":["https://openalex.org/I27837315"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Guojing Zhu","raw_affiliation_strings":["Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA,","institution_ids":["https://openalex.org/I27837315"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5036682320","display_name":"K\u00e4rt Tomberg","orcid":"https://orcid.org/0000-0002-6144-3601","observed_orcids":["https://orcid.org/0000-0002-6144-3601"]},"institutions":[{"id":"https://openalex.org/I27837315","display_name":"University of Michigan","ror":"https://ror.org/00jmfr291","country_code":"US","type":"education","lineage":["https://openalex.org/I27837315"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Kart Tomberg","raw_affiliation_strings":["Human Genetics, University of Michigan, Ann Arbor, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Human Genetics, University of Michigan, Ann Arbor, USA,","institution_ids":["https://openalex.org/I27837315"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5108264849","display_name":"David R. Siemieniak","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1344073410","display_name":"Howard Hughes Medical Institute","ror":"https://ror.org/006w34k90","country_code":"US","type":"facility","lineage":["https://openalex.org/I1344073410"]},{"id":"https://openalex.org/I27837315","display_name":"University of Michigan","ror":"https://ror.org/00jmfr291","country_code":"US","type":"education","lineage":["https://openalex.org/I27837315"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David R. Siemieniak","raw_affiliation_strings":["Life Sciences Institute, Howard Hughes Medical Institute and University of Michigan, Ann Arbor, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Life Sciences Institute, Howard Hughes Medical Institute and University of Michigan, Ann Arbor, USA,","institution_ids":["https://openalex.org/I1344073410","https://openalex.org/I27837315"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5063050675","display_name":"Sara Haynes","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I27837315","display_name":"University of Michigan","ror":"https://ror.org/00jmfr291","country_code":"US","type":"education","lineage":["https://openalex.org/I27837315"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Sara A. Haynes","raw_affiliation_strings":["Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA,","institution_ids":["https://openalex.org/I27837315"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5073421716","display_name":"Jishu Xu","orcid":"https://orcid.org/0000-0002-3679-6579","observed_orcids":["https://orcid.org/0000-0002-3679-6579","https://orcid.org/0000-0002-3139-5194"]},"institutions":[{"id":"https://openalex.org/I27837315","display_name":"University of Michigan","ror":"https://ror.org/00jmfr291","country_code":"US","type":"education","lineage":["https://openalex.org/I27837315"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Jishu Xu","raw_affiliation_strings":["Human Genetics, University of Michigan, Ann Arbor, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Human Genetics, University of Michigan, Ann Arbor, USA,","institution_ids":["https://openalex.org/I27837315"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5075444455","display_name":"Jun Z. Li","orcid":"https://orcid.org/0000-0001-6727-0812","observed_orcids":["https://orcid.org/0000-0001-6727-0812"]},"institutions":[{"id":"https://openalex.org/I27837315","display_name":"University of Michigan","ror":"https://ror.org/00jmfr291","country_code":"US","type":"education","lineage":["https://openalex.org/I27837315"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Jun Z. Li","raw_affiliation_strings":["Human Genetics, University of Michigan, Ann Arbor, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Human Genetics, University of Michigan, Ann Arbor, USA,","institution_ids":["https://openalex.org/I27837315"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5071223660","display_name":"David Ginsburg","orcid":"https://orcid.org/0000-0002-6436-8942","observed_orcids":["https://orcid.org/0000-0002-6436-8942"]},"institutions":[{"id":"https://openalex.org/I1344073410","display_name":"Howard Hughes Medical Institute","ror":"https://ror.org/006w34k90","country_code":"US","type":"facility","lineage":["https://openalex.org/I1344073410"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David Ginsburg","raw_affiliation_strings":["Howard Hughes Medical Institute, Ann Arbor, MI, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Howard Hughes Medical Institute, Ann Arbor, MI, USA","institution_ids":["https://openalex.org/I1344073410"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5036682320","https://openalex.org/A5063050675","https://openalex.org/A5073421716","https://openalex.org/A5075444455","https://openalex.org/A5088882561","https://openalex.org/A5101056654"],"corresponding_institution_ids":["https://openalex.org/I27837315"],"apc_list":{"value":5500,"currency":"USD","value_usd":5500},"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.31882516,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"120","issue":"21","first_page":"493","last_page":"493"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10881","display_name":"Blood Coagulation and Thrombosis Mechanisms","score":0.9940999746322632,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10881","display_name":"Blood Coagulation and Thrombosis Mechanisms","score":0.9940999746322632,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10746","display_name":"Platelet Disorders and Treatments","score":0.002300000051036477,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11280","display_name":"Hemophilia Treatment and Research","score":0.000699999975040555,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/factor-v-leiden","display_name":"factor V Leiden","score":0.9679999947547913},{"id":"https://openalex.org/keywords/venous-thrombosis","display_name":"venous thrombosis","score":0.8949999809265137},{"id":"https://openalex.org/keywords/arp2","display_name":"Arp2","score":0.7440000176429749},{"id":"https://openalex.org/keywords/arp2-3-complex","display_name":"Arp2/3 complex","score":0.9649999737739563},{"id":"https://openalex.org/keywords/synthetic-lethality","display_name":"synthetic lethality","score":0.6759999990463257},{"id":"https://openalex.org/keywords/modifier-genes","display_name":"genetic modifiers","score":0.6470000147819519},{"id":"https://openalex.org/keywords/enu-mutagenesis-screen","display_name":"ENU mutagenesis screen","score":0.843999981880188},{"id":"https://openalex.org/keywords/loss-of-function-variants","display_name":"loss-of-function mutations","score":0.6449999809265137},{"id":"https://openalex.org/keywords/actin-cytoskeleton","display_name":"actin cytoskeleton","score":0.6830000281333923}],"concepts":[{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.7320429682731628},{"id":"https://openalex.org/C75563809","wikidata":"https://www.wikidata.org/wiki/Q2656896","display_name":"Missense mutation","level":4,"score":0.6291905045509338},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.5927100777626038},{"id":"https://openalex.org/C2777175894","wikidata":"https://www.wikidata.org/wiki/Q185986","display_name":"Factor V Leiden","level":4,"score":0.5789754986763},{"id":"https://openalex.org/C76818968","wikidata":"https://www.wikidata.org/wiki/Q181940","display_name":"Sanger sequencing","level":4,"score":0.571257472038269},{"id":"https://openalex.org/C16671776","wikidata":"https://www.wikidata.org/wiki/Q5420592","display_name":"Exome sequencing","level":4,"score":0.5338659882545471},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.522478461265564},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.45773956179618835},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.35062462091445923},{"id":"https://openalex.org/C2780011451","wikidata":"https://www.wikidata.org/wiki/Q2751330","display_name":"Venous thrombosis","level":3,"score":0.18279233574867249},{"id":"https://openalex.org/C2780868729","wikidata":"https://www.wikidata.org/wiki/Q261327","display_name":"Thrombosis","level":2,"score":0.1318109929561615},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.11054709553718567},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.10671013593673706}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood.v120.21.493.493","doi":"https://doi.org/10.1182/blood.v120.21.493.493","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v120.21.493.493","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9537000060081482}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2538371258","https://openalex.org/W2949099637","https://openalex.org/W2979720067","https://openalex.org/W2953267252","https://openalex.org/W2994780302","https://openalex.org/W3157845616","https://openalex.org/W6921703795","https://openalex.org/W2516168736","https://openalex.org/W2113574769","https://openalex.org/W94943216"],"abstract_inverted_index":{"Abstract":[0,1],"493":[2],"Only":[3],"\u223c10%":[4],"of":[5,88,112,135,137,161,176,183,240,259,263,288,329,365,381,415,418,429,452],"individuals":[6],"carrying":[7],"the":[8,38,82,138,142,190,200,210,231,238,241,257,345,382,413,450],"common":[9],"risk":[10,402],"factor,":[11],"Factor":[12],"V":[13],"Leiden":[14],"(FVL),":[15],"will":[16],"develop":[17],"venous":[18],"thrombosis.":[19],"In":[20],"order":[21],"to":[22,78,102,117,192,368,445],"identify":[23,79,408],"potential":[24],"FVL":[25,48,212],"modifier":[26,213],"genes,":[27],"we":[28],"performed":[29,62,129,302],"a":[30,113,131,158,181,225,286,374],"sensitized":[31],"dominant":[32,211],"ENU":[33],"mutagenesis":[34],"screen":[35,60],"based":[36],"on":[37,130,303,425],"perinatal":[39],"synthetic":[40],"lethal":[41,83,384],"thrombosis":[42,401],"observed":[43],"in":[44,151,171,180,199,204,214,220,224,230,315,353,373,376,393,403],"mice":[45,68,99,108,184,357],"homozygous":[46,293],"for":[47,52,237,247,256,359,412],"(FVQ/Q)":[49],"and":[50,251,291,307,319,332,344,405,449],"hemizygous":[51],"tissue":[53],"factor":[54],"pathway":[55],"inhibitor":[56],"deficiency":[57,294,364],"(Tfpi+/\u2212).":[58],"The":[59],"was":[61,128],"by":[63],"crossing":[64],"ENU-treated":[65],"male":[66],"FVQ/Q":[67,84,97,105,121,385],"with":[69,81],"FVQ/+":[70],"Tfpi+/\u2212":[71,85,98,106,122,386],"females.":[72],"Surviving":[73],"G1":[74,90,107],"offspring":[75,91],"were":[76,350],"analyzed":[77],"survivors":[80],"genotype.":[86],"Analysis":[87,262],"7,128":[89],"(\u223c2X":[92],"genome":[93],"coverage)":[94],"identified":[95],"98":[96],"that":[100,189,283,292,391],"survived":[101],"weaning.":[103],"Fourteen":[104],"exhibited":[109],"successful":[110],"transmission":[111],"putative":[114],"suppressor":[115],"mutation":[116,194,218,290],"two":[118],"or":[119,325,395,431],"more":[120],"G2":[123],"offspring.":[124],"Whole":[125],"exome":[126,147],"sequencing":[127],"progeny":[132,207,265],"tested":[133],"member":[134],"8":[136],"14":[139,304],"lines":[140],"using":[141],"Agilent":[143],"SureSelect":[144],"mouse":[145,280],"whole":[146],"capture":[148],"kit":[149],"resulting":[150,372],"\u223c100":[152],"fold":[153],"coverage.":[154],"Variant":[155],"analysis":[156],"revealed":[157,274,311],"small":[159],"number":[160],"high":[162],"confidence":[163],"novel":[164,409],"heterozygous":[165,306,355],"(dominant)":[166],"single":[167],"nucleotide":[168],"variants":[169],"(SNVs)":[170],"each":[172,360],"sample.":[173],"Sanger":[174],"re-sequencing":[175],"all":[177],"11":[178,196],"SNVs":[179],"cohort":[182],"from":[185,266,443],"line":[186],"1":[187],"confirmed":[188],"G":[191],"C":[193],"(chromosome":[195],"base":[197],"19,977,300)":[198],"Actr2":[201,305,354],"gene":[202],"(present":[203],"15/16":[205],"re-sequenced":[206],"p<0.0001)":[208],"is":[209,235,245,254,285,295],"this":[215,416],"line.":[216],"This":[217],"resulted":[219],"an":[221,267,426],"R286G":[222,284],"substitution":[223],"highly":[226],"conserved":[227],"amino":[228],"acid":[229],"Arp2":[232,268,271,278,366,394],"protein,":[233],"which":[234,253],"essential":[236],"function":[239,289],"Arp2/3":[242,244],"complex.":[243],"responsible":[246],"intracellular":[248],"actin":[249],"branching":[250],"polymerization,":[252],"critical":[255],"regulation":[258],"cell":[260,322],"shape.":[261],"31":[264],"R/G":[269,272],"\u00d7":[270],"cross":[273],"only":[275],"one":[276],"live":[277],"G/G":[279],"(p<0.05),":[281],"suggesting":[282],"loss":[287],"lethal.":[296],"Complete":[297],"blood":[298,321],"counts":[299],"(Advia":[300],"2120)":[301],"10":[308],"wildtype":[309],"littermates":[310],"no":[312],"significant":[313],"differences":[314],"platelet":[316,330,337,340,346,370],"count,":[317],"red":[318],"white":[320],"counts,":[323],"hematocrit":[324],"hemoglobin.":[326],"However,":[327],"measurements":[328],"size":[331,333],"distribution":[334,342,348],"including":[335],"mean":[336],"dry":[338],"mass,":[339],"volume":[341],"width":[343,349],"component":[347],"significantly":[351],"altered":[352],"mutant":[356],"(p<0.05":[358],"measure).":[361],"Thus,":[362],"partial":[363],"appears":[367],"alter":[369],"structure/function":[371],"shift":[375],"hemostatic":[377],"balance":[378],"facilitating":[379],"survival":[380],"otherwise":[383],"phenotype.":[387],"These":[388],"results":[389],"suggest":[390],"variation":[392],"related":[396],"genes":[397],"could":[398],"potentially":[399],"modify":[400],"humans,":[404],"might":[406],"also":[407],"therapeutic":[410],"targets":[411],"treatment":[414],"class":[417],"disorders.":[419],"Disclosures:":[420],"Ginsburg:":[421],"Shire":[422],"Pharmaceuticals:":[423,435,441,458],"Membership":[424],"entity's":[427],"Board":[428],"Directors":[430],"advisory":[432],"committees;":[433],"Portola":[434],"Consultancy;":[436,439],"Catalyst":[437],"Biosciences:":[438],"Baxter":[440],"benefit":[442],"payments":[444],"Children's":[446],"Hosptial,":[447],"Boston,":[448],"University":[451],"Michigan":[453],"Patents":[454],"&":[455],"Royalties;":[456],"Merck":[457],"Consultancy.":[459]},"counts_by_year":[],"updated_date":"2026-10-17T09:40:24.721904","created_date":"2016-10-21T00:00:00"}
