Isenmann S, Brandner S, Aguzzi A
Institute of Neuropathology, University Hospital, Zürich, Switzerland.
Histol Histopathol. 1996 Oct;11(4):1063-73.
Transgenic and knockout mice have contributed much to our current understanding of the role played by single genes during development and in pathological processes of the CNS, such as neuro-degeneration. However, embryonic lethality resulting from the disruption of important genes has often hindered the interpretation of such experiments. Grafting of immature cells from genetically modified organisms into healthy recipients promises to efficiently bypass this problem. We have used neural transplantation techniques which allow us to keep CNS tissue of knockout and transgenic mice viable for a prolonged period of time in the brain or in the kidney capsule of healthy recipients. We have characterized biological parameters such as growth, proliferation and differentiation and also the formation of an intact blood-brain barrier (BBB) after grafting of wild-type telencephalic anlage in this system. We have also employed this technique to study the longterm properties of neuroepithelial tissue derived from knockout mice. The results of our studies are discussed in the context of neurodegenerative diseases.
转基因小鼠和基因敲除小鼠极大地促进了我们目前对单个基因在中枢神经系统(CNS)发育及病理过程(如神经退行性变)中所起作用的理解。然而,重要基因的破坏导致的胚胎致死性常常阻碍了此类实验结果的解读。将基因修饰生物体的未成熟细胞移植到健康受体中有望有效规避这一问题。我们运用了神经移植技术,该技术使我们能够让基因敲除小鼠和转基因小鼠的中枢神经系统组织在健康受体的脑内或肾被膜中长期存活。我们已经对诸如生长、增殖、分化等生物学参数以及在该系统中移植野生型端脑原基后完整血脑屏障(BBB)的形成进行了表征。我们还利用该技术研究了基因敲除小鼠来源的神经上皮组织的长期特性。我们将在神经退行性疾病的背景下讨论我们的研究结果。