Genetic increase in serum insulin-like growth factor-I (IGF-I) in C3H/HeJ compared with C57BL/6J mice is associated with increased transcription from the IGF-I exon 2 promoter
Genetic increase in serum insulin-like growth factor-I (IGF-I) in C3H/HeJ compared with C57BL/6J mice is associated with increased transcription from the IGF-I exon 2 promoter
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DOI：
10.1210/en.2005-0742
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发表时间：
2006-06-01
期刊：
影响因子：
4.8
通讯作者：
Rosen, Clifford J.
中科院分区：
文献类型：
--
作者：
Adamo, Martin L.;Ma, Xiuye;Rosen, Clifford J.
C3H/HeJ (C3H) 小鼠的血清 IGF-I 比 C57BL/6J (B6) 小鼠高 30 - 40%，这与骨矿物质密度和强度增加相关。这些差异是遗传性的，因此为确定血清 IGF-I 遗传变异和下游作用的分子机制提供了模型。我们现在报道，C3H 小鼠血清 IGF-I 的增加与雌性和雄性小鼠肝脏中次要外显子 2 启动子的转录增加有关。由外显子2启动子转录的IGF-I mRNA丰度增加引起的肝脏IGF-I基因表达的增加可以定量地解释C3H小鼠中血清IGF-I的增加。此外，雄性 C3H 小鼠肝脏中 Ea 和 Eb IGF-I mRNA 的水平均增加。禁食降低了两种品系雌性小鼠的血清 IGF-I 和肝脏 IGF-I mRNA 水平。然而，与禁食的 B6 小鼠相比，禁食的 C3H 小鼠的血清 IGF-I 和肝脏 IGF-I mRNA 水平仍然较高。在 C3H 小鼠的骨骼肌、脂肪、卵巢和肾脏中，从外显子 2 起始的 IGF-I 转录物水平也显着增加。 C3H 小鼠肌肉和脂肪中的 IGF 结合蛋白 (IGFBP)-5 mRNA 水平显着高于 B6 小鼠。雄性和雌性 C3H 小鼠的整个股骨中含有外显子 1 的转录物水平增加。我们得出的结论是，在 C3H 小鼠中，IGF-I 基因的转录增加以启动子和组织特异性方式发生。脂肪和肌肉中 IGF 结合蛋白 5 mRNA 水平的增加表明 C3H 小鼠这些组织中 IGF-I 信号传导增加。
C3H/HeJ (C3H) mice exhibit 30 - 40% higher serum IGF-I than do C57BL/6J (B6) mice, in association with increased bone mineral density and strength. These differences are inherited and thus provide a model for determining molecular mechanisms for genetic variation of serum IGF-I and downstream actions. We now report that increased serum IGF-I in C3H mice is associated with increased transcription from the minor exon 2 promoter in liver from female and male mice. The increase in hepatic IGF-I gene expression caused by increased abundance of IGF-I mRNA transcribed from the exon 2 promoter can quantitatively account for the increased serum IGF-I in C3H mice. Also, levels of both Ea and Eb IGF-I mRNAs are increased in livers of male C3H mice. Fasting lowered serum IGF-I and liver IGF-I mRNA levels in female mice of both strains. However, serum IGF-I and liver IGF-I mRNA levels remained higher in fasted C3H mice compared with fasted B6 mice. Levels of IGF-I transcripts initiated from exon 2 are also significantly increased in skeletal muscle, fat, ovaries, and kidneys of C3H mice. IGF binding protein (IGFBP)-5 mRNA levels are significantly higher in muscle and fat of C3H mice than in B6 mice. Levels of exon 1-containing transcripts are increased in whole femurs of male and female C3H mice. We conclude that increased transcription of the IGF-I gene occurs in a promoter- and tissue-specific manner in C3H mice. The increased IGF binding protein-5 mRNA levels in fat and muscle suggest that IGF-I signaling is increased in these tissues in C3H mice.