title: Trisomy of Erg is required for myeloproliferation in a mouse model of Down syndrome.
abstract: Down syndrome is characterized by multiple phenotypic manifestations associated with trisomy of chromosome 21. The transient myeloproliferative disorder and acute megakaryocytic leukemia associated with Down syndrome are uniquely associated with mutations in the transcription factor GATA1; however, the identity of trisomic genes on chromosome 21 that predispose to these hematologic disorders remains unknown. Using a loss-of-function allele, we show that specific reduction to functional disomy of the Erg gene corrects the pathologic and hematologic features of myeloproliferation in the Ts(17(16))65Dn mouse model of Down syndrome, including megakaryocytosis and progenitor cell expansion. Our data provide genetic evidence establishing the need for Erg trisomy for myeloproliferation in Ts(17(16))65Dn mice and imply that increased ERG gene dosage may be a key consequence of trisomy 21 that can predispose to malignant hematologic disorders in Down syndrome.
authors.affiliation: Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
authors.forename: Ashley P
authors.initials: AP
authors.lastname: Ng
authors.forename: Craig D
authors.initials: CD
authors.lastname: Hyland
authors.forename: Donald
authors.initials: D
authors.lastname: Metcalf
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Carmichael
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Loughran
authors.forename: Ladina
authors.initials: L
authors.lastname: Di Rago
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Kile
authors.forename: Warren S
authors.initials: WS
authors.lastname: Alexander
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020125:Mutation, Missense / Q000235:genetics; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics*; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; D014314:Trisomy / Q000235:genetics* / Q000473:pathology
chemical_list: C531115:ERG protein, mouse; D015513:Oncogene Proteins; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG