Analysis of C-MYC function in normal cells via conditional gene-targeted mutation
Analysis of C-MYC function in normal cells via conditional gene-targeted mutation
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DOI：
10.1016/s1074-7613(01)00088-7
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发表时间：
2001-01-01
期刊：
影响因子：
32.4
通讯作者：
Alt, FW
中科院分区：
文献类型：
--
作者：
de Alboran, IM;O'Hagan, RC;Alt, FW
小鼠c-myc基因的种系失活导致胚胎死亡。因此，我们开发了一种基于LoxP/Cre的条件突变方法来测试c-myc在小鼠胚胎成纤维细胞（MEFs）和成熟B淋巴细胞中的作用。Cre表达导致野生型MEFs增殖减少，但c-Myc缺陷型MEFs表现出进一步减少。与成纤维细胞相反，Cre表达对野生型B细胞增殖没有明显影响。B细胞中两种c-Myc基因的缺失导致对抗-CD 40加IL-4的应答的增殖严重受损。然而，经处理的细胞确实上调了几种早期活化标志物，但不上调CD 95或CD 95配体。我们讨论了这些发现与潜在的c-Myc在增殖和凋亡的功能，并讨论了潜在的限制，在铬介导的基因失活的方法。
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.