To study oncogenesis in the erythroid lineage, we have generated transgenic mice carrying the human c-MYC proto-oncogene under the control of mouse GATA-1 regulatory sequences. Six transgenic lines expressed the transgene and displayed a clear oncogenic phenotype. Of these, five developed an early onset, rapidly progressive erythroleukemia that resulted in death of the founder animals 30-50 d after birth. Transgenic progeny of the sixth founder, while also expressing the transgene, remained asymptomatic for more than 8 mo, whereupon members of this line began to develop late onset erythroleukemia. The primary leukemic cells were transplantable into nude mice and syngeneic hosts. Cell lines were established from five of the six leukemic animals and these lines, designated erythroleukemia/c-MYC (EMY), displayed proerythroblast morphology and expressed markers characteristic of the erythroid lineage, including the erythropoietin receptor and beta-globin. Moreover, they also manifested a limited potential to differentiate in response to erythropoietin. Studies in the surviving transgenic line indicated that, contrary to our expectations, the transgene was not expressed in the mast cell lineage. That, coupled with the exclusive occurrence of erythroleukemia in all the transgenic lines, suggests that the GATA-1 promoter construct we have used includes regulatory sequences necessary for in vivo erythroid expression only. Additional sequences would appear to be required for expression in mast cells. Further, our results show that c-MYC can efficiently transform erythroid precursors if expressed at a vulnerable stage of their development.
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1 May 1995
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May 01 1995
Expression of c-MYC under the control of GATA-1 regulatory sequences causes erythroleukemia in transgenic mice.
R C Skoda,
R C Skoda
Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
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S F Tsai,
S F Tsai
Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
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S H Orkin,
S H Orkin
Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
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P Leder
P Leder
Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
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R C Skoda
Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
S F Tsai
Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
S H Orkin
Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
P Leder
Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1995) 181 (5): 1603–1613.
Citation
R C Skoda, S F Tsai, S H Orkin, P Leder; Expression of c-MYC under the control of GATA-1 regulatory sequences causes erythroleukemia in transgenic mice.. J Exp Med 1 May 1995; 181 (5): 1603–1613. doi: https://doi.org/10.1084/jem.181.5.1603
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