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Immunity. 2001 Jan;14(1):45-55.

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

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1
Howard Hughes Medical Institute and Children's, Hospital, Center for Blood Research and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

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.

PMID:
11163229
[Indexed for MEDLINE]
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