MDM2 overexpression generates a skin phenotype in both wild type and p53 null mice
MDM2 overexpression generates a skin phenotype in both wild type and p53 null mice
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DOI：
10.1038/sj.onc.1202448
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发表时间：
1999-02-18
期刊：
影响因子：
8
通讯作者：
Wasylyk, B
中科院分区：
文献类型：
--
作者：
Alkhalaf, M;Ganguli, G;Wasylyk, B
MDM2原癌基因在人类肿瘤中过表达，并调节肿瘤抑制基因p53和pRb的活性。我们在CMV启动子的控制下创造了过表达MDM2的小鼠。这些小鼠并没有表现出肿瘤发病率的增加，而是一种特殊的皮肤表型，其特征是脱皮和过度角化。研究发现，转基因MDM2在正常情况下高水平表达MDM2的表皮组织中过表达。表型在出生后第一周出现，然后随着年龄的增长而减少，与转基因的表达水平密切相关。MDM2的过度表达与基底层增殖增加、表皮增厚、分化标志细胞角蛋白CK14、CK10和CK1的表达改变以及含有分化产物的颗粒的大小和数量减少有关。P53缺失背景下的转基因小鼠表现出相似但不相同的变化，表明MDM2的作用在一定程度上是P53非依赖的。皮肤是小鼠MDM2表达的主要部位，这增加了MDM2过度表达扰乱MDM2正常表达模式并抑制表皮分化的可能性。
The MDM2 proto-oncogene is overexpressed in human tumours and regulates the activities of the tumour suppressors p53 and pRB We created mice that overexpress MDM2 under the control of the CMV promoter. These mice did not display an increased tumour incidence, but rather a specific skin phenotype, characterized by desquamation and hyperkeratosis. Transgenic MDM2 was found to be overexpressed in the epidermis, a tissue that normally expresses high levels of MDM2. The phenotype appeared during the first week after birth and then lessened with age, closely following the level of expression of the transgene. MDM2 overexpression was associated with an increase in proliferation in the basal layer, thickening of the epidermis, altered expression of the differentiation markers cytokeratin CK14, CK10 and CK1, and a decrease in the size and the number of granules that contain products of differentiation. Transgenic mice on a p53 null background displayed similar although not identical changes, showing that the effects of MDM2 are to a certain degree p53 independent. The skin is a major site of MDM2 expression in mice, raising the possibility that MDM2 overexpression perturbs the normal pattern of MDM2 expression and inhibits differentiation of the epidermis.