Abstract
Germline inactivation of c-myc in mice causes embryonic lethality. Therefore, we developed a LoxP/Cre-based conditional mutation approach to test the role of c-myc in mouse embryonic fibroblasts (MEFs) and mature B lymphocytes. Cre expression resulted in reduced proliferation of wild-type MEFs, but c-Myc-deficient MEFs showed a further reduction. In contrast to fibroblasts, Cre expression had no apparent affect on wild-type B cell proliferation. Deletion of both c-Myc genes in B cells led to severely impaired proliferation in response to anti-CD40 plus IL-4. However, treated cells did upregulate several early activation markers but not CD95 or CD95 ligand. We discuss these findings with respect to potential c-Myc functions in proliferation and apoptosis and also discuss potential limitations in the Cre-mediated gene inactivation approach.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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B-Lymphocytes / cytology
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B-Lymphocytes / drug effects
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B-Lymphocytes / metabolism
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B-Lymphocytes / physiology
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CD40 Antigens / immunology
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Cell Cycle
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Cell Cycle Proteins*
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Cells, Cultured
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclin-Dependent Kinases / antagonists & inhibitors
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Fibroblasts / cytology
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Fibroblasts / metabolism
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G1 Phase
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Gene Targeting
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Interleukin-4 / immunology
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Interleukin-4 / pharmacology
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Lymphocyte Activation
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Mice
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Mice, Inbred C57BL
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Microtubule-Associated Proteins / metabolism
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Mitogens / immunology
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Mitogens / pharmacology
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Mutation
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism
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Proto-Oncogene Proteins c-myc / physiology*
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Resting Phase, Cell Cycle
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Tumor Suppressor Proteins*
Substances
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CD40 Antigens
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Cdkn1b protein, mouse
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Cell Cycle Proteins
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Microtubule-Associated Proteins
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Mitogens
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Proto-Oncogene Proteins c-myc
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Tumor Suppressor Proteins
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Cyclin-Dependent Kinase Inhibitor p27
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Interleukin-4
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Cyclin-Dependent Kinases