Herzog K H, Chen S C, Morgan J I
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
J Neurosci. 1999 Jun 1;19(11):4349-59. doi: 10.1523/JNEUROSCI.19-11-04349.1999.
Although a number of studies have implicated c-Jun in neuronal death and axonal regeneration, it is unknown whether Jun function is essential for either response. One approach to resolve this issue is to analyze knock-out mice. However, c-jun-null mice die at midgestation, precluding critical investigation. Therefore, a xenograft paradigm was used in which retinas from embryonic day 12.5 (E12.5) c-jun nullizygous or wild-type mice were transplanted onto the superior colliculus of newborn rats. The rats were allowed to develop, and the grafts were assayed at various times for cell death and axon growth. Histologically, grafts of both genotypes developed in identical manners and had morphological characteristics of retinas. A functional c-jun allele was not essential for axogenesis, because ganglion cells in retinal grafts from c-jun nullizygous mice developed axons that projected into the colliculus. Programmed cell death (PCD) was also evident in the age-appropriate regions of the retina in both wild-type and c-jun-null grafts. Furthermore, there were no discernible differences in the number or location of dying cells in the two genotypes. That c-jun was not essential for PCD was supported by two additional findings. First, a c-jun-lacZ reporter gene was expressed in many cells in developing and grafted retinas, although only a few of these cells were destined to die. Second, in E12.5 c-jun-null embryos there were normal levels of PCD in the trigeminal ganglion. Together, these data indicate that c-Jun is not essential for axon growth in the retina or for PCD in the retina and trigeminal ganglion.
尽管多项研究表明c-Jun与神经元死亡和轴突再生有关,但尚不清楚Jun的功能对于这两种反应是否必不可少。解决这个问题的一种方法是分析基因敲除小鼠。然而,c-jun基因缺失的小鼠在妊娠中期死亡,无法进行关键研究。因此,采用了一种异种移植模式,将胚胎第12.5天(E12.5)的c-jun基因纯合缺失或野生型小鼠的视网膜移植到新生大鼠的上丘。让大鼠发育,并在不同时间检测移植组织的细胞死亡和轴突生长情况。从组织学上看,两种基因型的移植组织发育方式相同,具有视网膜的形态特征。功能性c-jun等位基因对于轴突形成并非必不可少,因为来自c-jun基因纯合缺失小鼠的视网膜移植组织中的神经节细胞长出了投射到上丘的轴突。程序性细胞死亡(PCD)在野生型和c-jun基因缺失移植组织的视网膜中与年龄相符的区域也很明显。此外,两种基因型中死亡细胞的数量和位置没有明显差异。另外两个发现支持了c-jun对于PCD并非必不可少的观点。第一,c-jun-lacZ报告基因在发育中和移植后的视网膜中的许多细胞中表达,尽管这些细胞中只有少数注定会死亡。第二,在E12.5的c-jun基因缺失胚胎中,三叉神经节中的PCD水平正常。总之,这些数据表明c-Jun对于视网膜中的轴突生长或视网膜和三叉神经节中的PCD并非必不可少。