Mouse embryos and chimera cloned from neural cells in the postnatal cerebral cortex
Mouse embryos and chimera cloned from neural cells in the postnatal cerebral cortex
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DOI：
10.1089/clo.2005.7.45
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发表时间：
2005-03-01
期刊：
影响因子：
--
通讯作者：
Yagi, T
中科院分区：
文献类型：
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作者：
Makino, H;Yamazaki, Y;Yagi, T
小鼠的克隆是通过将各种类型的体细胞核转移到去核卵母细胞中来实现的。然而，所有利用成年大脑皮层神经元细胞核生产活体克隆后代的尝试都失败了。此前，我们利用从胎儿大脑皮层收集的神经细胞核获得了克隆小鼠。在这里，我们尝试使用出生后（第 0-4 天）小鼠大脑皮层的分化神经元来生成克隆小鼠。尽管我们无法获得活的克隆幼崽，但许多胎儿已经发育到了 10.5 天。这些胎儿表现出神经上皮呈球形缺失、神经管管腔塌陷、神经元标记蛋白表达异常等多种异常。我们培育了嵌合小鼠，其中一些毛细胞和肾细胞源自分化的神经元。在嵌合胎儿中，LacZ 阳性供体细胞位于所有三个生殖细胞层中。然而，没有获得供体来源细胞贡献较大的嵌合体。这些结果表明分化神经元的细胞核已经失去了发育全能性。换句话说，传统的核移植技术不允许分化的神经元的细胞核进行正常胚胎发育所需的完整基因组重编程。
Cloning of mice has been achieved by transferring nuclei of various types of somatic cell nuclei into enucleated oocytes. However, all attempts to produce live cloned offspring using the nuclei of neurons from adult cerebral cortex have failed. Previously we obtained cloned mice using the nuclei of neural cells collected from fetal cerebral cortex. Here, we attempted to generate cloned mice using differentiated neurons from the cerebral cortex of postnatal (day 0-4) mice. Although we were unable to obtain live cloned pups, many fetuses reached day 10.5 days of development. These fetuses showed various abnormalities such as spherical omission of the neuroepithelium, collapsed lumen of neural tube, and aberrant expressions of marker proteins of neurons. We produced chimeric mice in which some hair cells and kidney cells were originated from differentiated neurons. In chimeric fetuses, LacZ-positive donor cells were in all three germ cell layers. However, chimeras with large contribution of donor-derived cells were not obtained. These results indicate that nuclei of differentiated neurons have lost their developmental totipotency. In other words, the conventional nuclear transfer technique does not allow nuclei of differantiated neurons to undergo complete genomic reprogramming required for normal embryonic development.