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

被引：330

作者：

de Alboran, IM

O'Hagan, RC

Gärtner, F

Malynn, B

Davidson, L

Rickert, R

Rajewsky, K

DePinho, RA

Alt, FW ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Childrens Hosp, Ctr Blood Res, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[4] Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA

[5] Univ Cologne, Inst Genet, D-50931 Cologne, Germany

[6] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA

来源：

IMMUNITY | 2001年 / 14卷 / 01期

关键词：

D O I：

10.1016/S1074-7613(01)00088-7

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：45 / 55

页数：11

共 60 条

[51] IDENTIFICATION OF A MYC-DEPENDENT STEP DURING THE FORMATION OF ACTIVE G(1) CYCLIN-CDK COMPLEXES [J].