ABNORMAL BONE-GROWTH AND SELECTIVE TRANSLATIONAL REGULATION IN BASIC FIBROBLAST GROWTH-FACTOR (FGF-2) TRANSGENIC MICE
ABNORMAL BONE-GROWTH AND SELECTIVE TRANSLATIONAL REGULATION IN BASIC FIBROBLAST GROWTH-FACTOR (FGF-2) TRANSGENIC MICE
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DOI：
10.1091/mbc.6.12.1861
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发表时间：
1995-12-01
影响因子：
3.3
通讯作者：
DOETSCHMAN, T
中科院分区：
文献类型：
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作者：
COFFIN, JD;FLORKIEWICZ, RZ;DOETSCHMAN, T
碱性成纤维细胞生长因子（FGF-2）是一种多效性生长因子，存在于多种细胞和组织中。FGF-2通常在低水平合成，在各种病理中升高，最明显的是在癌症和损伤修复中。为了研究FGF-2升高的影响，在磷酸甘油酸激酶启动子的控制下，在转基因小鼠中表达了人全长cDNA。FGF-2的过度表达导致多种骨骼畸形，包括长骨变短、变平和中度大头畸形。通过Western blot比较，FGF-2转基因小鼠与非转基因小鼠在所有主要器官和组织中均有人类FGF-2蛋白的表达，包括脑、心、肺、肝、肾、脾和骨骼肌；然而，在不同的器官和组织中观察到不同的FGF-2蛋白亚型的摩尔比。一些组织优先合成较大的FGF-2亚型，而其他组织主要产生较小的18 kda FGF-2。高分子量异构体的翻译始于非常规的CUG密码子，而18kda异构体的翻译始于FGF-2 mRNA中的AUG密码子。因此，来自FGF-2转基因小鼠的Western blot数据表明，FGF-2亚型的组织特异性表达是通过翻译调控的。
Basic fibroblast growth factor (FGF-2) is a pleiotropic growth factor detected in many different cells and tissues. Normally synthesized at low levels, FGF-2 is elevated in various pathologies, most notably in cancer and injury repair. To investigate the effects of elevated FGF-2, the human full-length cDNA was expressed in transgenic mice under control of a phosphoglycerate kinase promoter. Overexpression of FGF-2 caused a variety of skeletal malformations including shortening and flattening of long bones and moderate macrocephaly. Comparison by Western blot of FGF-2 transgenic mice to nontransgenic littermates showed expression of human FGF-2 protein in all major organs and tissues examined including brain, heart, lung, liver, kidney, spleen, and skeletal muscle; however, different molar ratios of FGF-2 protein isoforms were observed between different organs and tissues. Some tissues preferentially synthesize larger isoforms of FGF-2 while other tissues produce predominantly smaller 18-kDa FGF-2. Translation of the high molecular weight isoforms initiates from unconventional CUG codons and translation of the 18-kDa isoform initiates from an AUG codon in the FGF-2 mRNA. Thus the Western blot data from the FGF-2 transgenic mice suggest that tissue-specific expression of FGF-2 isoforms is regulated translationally.