携带对编码胰岛素样生长因子I (Igf-1) 和1型IGF受体 (Igf1r) 的基因零突变的小鼠
J P Liu1, J Baker, A S Perkins
1Department of Genetics and Development, Columbia University, New York, New York 10032.
Cell
|October 8, 1993
概括
在小鼠中,胰岛素样生长因子 (IGF) 基因干扰导致生长缺陷. Igf1r基因对胚胎发育至关重要,缺少它会导致严重的生长缺陷和呼吸衰竭.
科学领域:
- 发育生物学是发展生物学.
- 遗传学 是一个遗传学.
- 内分泌学 在内分泌学.
背景情况:
- 胰岛素类生长因子 (IGF) 在哺乳动物的生长和发育中起着至关重要的作用.
- 之前的研究已经确定了Igf-1和Igf-2在产后生长中的重要性.
- 在胚胎发育中IGF受体 (Igf1r) 的作用需要进一步阐明.
研究的目的:
- 研究胰岛素样生长因子1 (Igf-1) 和其受体 (Igf1r) 在小鼠胚胎发育中的特定作用.
- 描述针对Igf-1,Igf-2和Igf1r的向基因破坏的表型后果.
- 了解胚胎发生过程中不同IGF信号组件之间的相互作用.
主要方法:
- 针对Igf-1,Igf-2和Igf1r进行向基因淘汰的小鼠的生成和表型分析.
- 创建和检查双重突变小鼠 (例如,Igf-1(-/-) /Igf1r(-/-),Igf-2(-) /Igf1r(-/-)).
- 对不同突变基因型的生长缺陷,器官发育和生存率的比较评估.
主要成果:
- Igf-1无突变体表现为矮体 (60%的正常出生体重),存活率可变.
- Igf1r无突变体表现出严重的生长缺陷 (45%的正常大小),由于呼吸衰竭而导致的胚胎死亡,以及器官缺血.
- 双重突变揭示了Igf1r是必不可少的,因为Igf-1(-/-) /Igf1r(-/-) 小鼠除了Igf1r(-/-之外没有其他表型,而Igf-2(-) /Igf1r(-/-) 和Igf-1(-/-) /Igf-2(-) 小鼠则有恶化的矮体 (30%的正常大小).
结论:
- 对于胚胎生存来说,Igf1r是不可或缺的,它介导着除了单独的Igf-1和Igf-2之外的基本功能.
- Igf-1和Igf-2有助于生长,但Igf1r信号是正常胚胎发育和活力的关键决定因素.
- 这些发现凸显了IGF信号元件在小鼠发育中的复杂和层次性的作用.
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