Germline inactivation of c-myc in mice causes embryonic lethality. Therefor
e, we developed a LoxP/Cre-based conditional mutation approach to test the
role of c-myc in mouse embryonic fibroblasts (MEFs) and mature B lymphocyte
s. 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 proliferat
ion in response to anti-CD40 plus IL-4. However, treated cells did upregula
te 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 ge
ne inactivation approach.