Muscle-specific cell ablation conditional upon Cre-mediated DNA recombination in transgenic mice leads to massive spinal and cranial motoneuron loss
Muscle-specific cell ablation conditional upon Cre-mediated DNA recombination in transgenic mice leads to massive spinal and cranial motoneuron loss
复制标题
DOI：
10.1006/dbio.1997.8859
复制
发表时间：
1998-05-15
影响因子：
2.7
通讯作者：
Martin, GR
中科院分区：
文献类型：
--
作者：
Grieshammer, U;Lewandoski, M;Martin, GR
我们在这里描述了一种基于 Cre 介导的 DNA 重组的二元转基因系统，用于小鼠遗传细胞消融，使我们能够通过使两个表型正常的转基因系交配来获得骨骼肌缺陷的胚胎。在这些胚胎中，由于编码白喉毒素 A 片段的基因表达，骨骼肌被消除。细胞消融大约从胚胎第 12.5 天开始逐渐发生，到 E18.5 几乎所有骨骼肌都消失了。对肌细胞消融后果的分析表明，几乎所有脊髓运动神经元都被E18.5丢失，这提供了强有力的证据，证明胚胎发生期间脊髓运动神经元的存活依赖于来自其靶组织、骨骼肌的信号，并且非肌肉来源产生的营养信号足以支持在缺乏肌肉源性信号的情况下不超过10%的胚胎脊髓运动神经元的存活。在肌肉缺陷的胚胎中，颅骨（舌下和面部）运动神经元也大量损失，因此表明颅骨运动神经元的存活也依赖于其靶组织产生的营养信号。尽管脊髓运动神经元是脊髓中间神经元的主要目标，但运动神经元的损失并不影响中间神经元的存活。肌肉缺陷的胚胎有腭裂和下颌畸形，这增加了它们作为人类疾病罗宾序列的小鼠模型的可能性。这里报告的数据证明了二元转基因系统用于获得小鼠胚胎的效用，其中特定细胞群已被消除，以便可以研究其在胚胎发育中的作用。 (C) 1998 年学术出版社。
We describe here a binary transgenic system based on Cre-mediated DNA recombination for genetic cell ablation in mice that enabled us to obtain skeletal muscle-deficient embryos by mating two phenotypically normal transgenic lines. In those embryos, skeletal muscles are eliminated as a consequence of the expression of the gene encoding the diphtheria toxin A fragment. Cell ablation occurs gradually beginning approximately on embryonic day (E) 12.5, and by E18.5 almost all skeletal muscle is absent. Analysis of the consequences of muscle cell ablation revealed that almost all spinal motoneurons are lost by E18.5, providing strong evidence that survival of spinal motoneurons during embryogenesis is dependent on signals from their target tissue, skeletal muscle, and that trophic signals produced by nonmuscle Sources are sufficient to support survival of no more than 10% of embryonic spinal motoneurons in the absence of muscle-derived signals. There was also substantial loss of cranial (hypoglossal and facial) motoneurons in the muscle-deficient embryos, thus indicating that cranial motoneuron survival is also dependent on trophic signals produced by their target tissue. Although spinal motoneurons are a major target of spinal interneurons, the loss of motoneurons did not affect interneuron survival. Muscle-deficient embryos had a cleft palate and abnormalities of the lower jaw, raising the possibility that they might serve as a mouse model for the human disorder, Robin sequence. The data reported here demonstrate the utility of a binary transgenic system for obtaining mouse embryos in which a specific cell population has been ablated, so that its role in embryonic development can be studied. (C) 1998 Academic Press.