The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice
NaturePublished 1 December 1985
Jerry M. Adams, A. W. Harris, Carl A. Pinkert, Lynn M. Corcoran, Warren S. Alexander, Suzanne Cory
Citations1,785
SJR quartileQ1
SJR score18.29
SNIP10.16
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TL;DR
Transgenic mice bearing the cellular myc oncogene coupled to the immunoglobulin μ or κ enhancer frequently develop a fatal lymphoma within a few months of birth and constitutive c-myc expression appears to be highly leukaemogenic at several stages of B-cell maturation.
Abstract
Transgenic mice bearing the cellular myc oncogene coupled to the immunoglobulin mu or kappa enhancer frequently develop a fatal lymphoma within a few months of birth. Since the tumours represent represent both immature and mature B lymphocytes, constitutive c-myc expression appears to be highly leukaemogenic at several stages of B-cell maturation. These myc mice should aid study of lymphoma development, B-cell ontogeny and immunoglobulin regulation.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
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NatureTumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes
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CellCell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor
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CellImmunoglobulin gene transcription is activated by downstream sequence elements
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ScienceMetallothionein-Human GH Fusion Genes Stimulate Growth of Mice
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CellTwo mRNAs with different 3′ ends encode membrane-bound and secreted forms of immunoglobulin μ chain
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NatureMultiple arrangements of viral DNA and an activated host oncogene in bursal lymphomas
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PubMedLymphosarcoma: virus-induced thymic-independent disease in mice.
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NatureA lymphocyte-specific enhancer in the mouse immunoglobulin κ gene
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CellMurine T lymphomas in which the cellular myc oncogene has been activated by retroviral insertion
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Proceedings of the National Academy of SciencesCellular myc oncogene is altered by chromosome translocation to an immunoglobulin locus in murine plasmacytomas and is rearranged similarly in human Burkitt lymphomas.
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CellIntroduction of a μ immunoglobulin gene into the mouse germ line: Specific expression in lymphoid cells and synthesis of functional antibody
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NatureStructure of mouse metallothionein-I gene and its mRNA
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