Document Detail


Trisomy of Erg is required for myeloproliferation in a mouse model of Down syndrome.
MedLine Citation:
PMID:  20007548     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Ashley P Ng; Craig D Hyland; Donald Metcalf; Catherine L Carmichael; Stephen J Loughran; Ladina Di Rago; Benjamin T Kile; Warren S Alexander
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-09
Journal Detail:
Title:  Blood     Volume:  115     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-14     Completed Date:  2010-06-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3966-9     Citation Subset:  AIM; IM    
Affiliation:
Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal*
Down Syndrome / genetics*,  pathology
Female
Flow Cytometry
Male
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Knockout
Mutation, Missense / genetics
Myeloproliferative Disorders / genetics*,  pathology
Oncogene Proteins / genetics*
Trisomy / genetics*,  pathology
Chemical
Reg. No./Substance:
0/ERG protein, mouse; 0/Oncogene Proteins
Comments/Corrections
Comment In:
Blood. 2010 May 13;115(19):3859-60   [PMID:  20466869 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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