Analysis of C-MYC function in normal cells via conditional gene-targeted mutation

Immunity. 2001 Jan;14(1):45-55. doi: 10.1016/s1074-7613(01)00088-7.


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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / physiology
  • CD40 Antigens / immunology
  • Cell Cycle
  • Cell Cycle Proteins*
  • Cells, Cultured
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • G1 Phase
  • Gene Targeting
  • Interleukin-4 / immunology
  • Interleukin-4 / pharmacology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / metabolism
  • Mitogens / immunology
  • Mitogens / pharmacology
  • Mutation
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • Proto-Oncogene Proteins c-myc / physiology*
  • Resting Phase, Cell Cycle
  • Tumor Suppressor Proteins*


  • CD40 Antigens
  • Cdkn1b protein, mouse
  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • Mitogens
  • Proto-Oncogene Proteins c-myc
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Interleukin-4
  • Cyclin-Dependent Kinases