Expression of epidermal growth factor in transgenic mice causes growth retardation
Expression of epidermal growth factor in transgenic mice causes growth retardation
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DOI：
10.1074/jbc.m004189200
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发表时间：
2000-12-08
影响因子：
4.8
通讯作者：
Wong, RWC
中科院分区：
文献类型：
--
作者：
Chan, SY;Wong, RWC
表皮生长因子（EGF）家族的肽信号通过受体酪氨酸激酶erbB家族，并在发育和肿瘤发生中起重要作用。EGF和转化生长因子（TGF）-α都只与erbB 1结合并激活erbB 1。EGF的前体与TGF-α的前体不同，其具有8个额外的EGF样重复序列。我们最近表明，没有这些重复的EGF前体是生物活性的，并导致转基因小鼠精子生成不足。在这里，我们提出的证据表明，广泛表达这种工程EGF前体的转基因小鼠的生长也受到阻碍。这些小鼠出生时的体重一直是正常体重的一半，成年后达到正常体重的近80%。其机制涉及血清胰岛素样生长因子结合蛋白-3的减少。软骨细胞在生长板的发育受到影响，成骨细胞在骨内膜和骨膜中积聚。除了这些关于EGF对骨骼发育体内影响的新发现外，我们在转基因动物中没有观察到肿瘤形成的迹象。与以前关于TGF-α转基因小鼠的报道相反，我们发现EGF和TGF-α的生物学功能明显不同。
The epidermal growth factor (EGF) family of peptides signals through the erbB family of receptor tyrosine kinases and plays important roles in development and tumorigenesis. Both EGF and transforming growth factor (TGF)-alpha only bind to erbB1 and activate it. The precursor of EGF is distinct from that of TGF-alpha in having eight additional EGF-like repeats. We have recently shown that the EGF precursor without these repeats is biologically active and leads to hypospermatogenesis in transgenic mice. Here we present evidence that the growth of transgenic mice widely expressing this engineered EGF precursor is also stunted. These mice were consistently born at half the normal weight and reached almost 80% of normal weight at adulthood. The mechanism involved a reduction of serum insulin-like growth factor-binding protein-3. Chondrocyte development in the growth plate was affected, and osteoblasts accumulated in the endosteum and periosteum. Besides these novel findings on the in vivo effects of EGF on bone development, we observed no sign of tumor formation in our transgenic animals. In contrast to previous reports on TGF-alpha transgenic mice, we show that the biological functions of EGF and TGF-alpha are clearly distinct.