Trisomy of Erg is required for myeloproliferation in a mouse model of Down syndrome

• Published in: Blood Vol. 115; no. 19; pp. 3966 - 3969
• Main Authors: Ng, Ashley P., Hyland, Craig D., Metcalf, Donald, Carmichael, Catherine L., Loughran, Stephen J., Di Rago, Ladina, Kile, Benjamin T., Alexander, Warren S.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 13-05-2010; Americain Society of Hematology
• Subjects: Animals; Biological and medical sciences; Chromosome aberrations; Disease Models, Animal; Down Syndrome - genetics; Down Syndrome - pathology; Female; Flow Cytometry; Hematologic and hematopoietic diseases; Male; Medical genetics; Medical sciences; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Mutation, Missense - genetics; Myeloproliferative Disorders - genetics; Myeloproliferative Disorders - pathology; Oncogene Proteins - genetics; Transcription Factors; Transcriptional Regulator ERG; Trisomy - genetics; Trisomy - pathology; Chromosomal aberration; Animal model; Trisomy; Hematology; Rodentia; Chromosome G21; Aneuploidy; Down syndrome; Vertebrata; Mammalia; Mouse; C-Onc gene; Protooncogene
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2009-09-242107

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(1716)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(1716)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.