Hoyt P R, Bartholomew C, Davis A J, Yutzey K, Gamer L W, Potter S S, Ihle J N, Mucenski M L
University of Tennessee Graduate School of Biomedical Sciences, Biology Division, Oak Ridge National Laboratory, TN 37831-8080, USA.
Mech Dev. 1997 Jul;65(1-2):55-70. doi: 10.1016/s0925-4773(97)00057-9.
The ecotropic viral integration site-1 (Evi1) locus was initially identified as a common site of retroviral integration in myeloid tumors of the AKXD-23 recombinant inbred mouse strain. The full-length Evi1 transcript encodes a putative transcription factor, containing ten zinc finger motifs found within two domains of the protein. To determine the biological function of the Evi1 proto-oncogene, the full-length, but not an alternately spliced, transcript was disrupted using targeted mutagenesis in embryonic stem cells. Evi1 homozygous mutant embryos die at approximately 10.5 days post coitum. Mutants were distinguished at 10.5 days post coitum by widespread hypocellularity, hemorrhaging, and disruption in the development of paraxial mesenchyme. In addition, defects in the heart, somites, and cranial ganglia were detected and the peripheral nervous system failed to develop. These results correlated with whole-mount in situ hybridization analyses of embryos which showed expression of the Evi1 proto-oncogene in embryonic mesoderm and neural crest-derived cells associated with the peripheral nervous system. These data suggest that Evi1 has important roles in general cell proliferation, vascularization, and cell-specific developmental signaling, at midgestation.
嗜亲性病毒整合位点1（Evi1）基因座最初被确定为AKXD - 23重组近交小鼠品系髓系肿瘤中逆转录病毒整合的常见位点。全长Evi1转录本编码一种假定的转录因子，该蛋白在两个结构域内含有十个锌指基序。为了确定Evi1原癌基因的生物学功能，在胚胎干细胞中使用靶向诱变破坏了全长转录本（而非可变剪接转录本）。Evi1纯合突变胚胎在交配后约10.5天死亡。在交配后10.5天，突变体表现为广泛的细胞减少、出血以及轴旁间充质发育紊乱。此外，还检测到心脏、体节和颅神经节的缺陷，并且外周神经系统未能发育。这些结果与胚胎的整体原位杂交分析相关，该分析显示Evi1原癌基因在与外周神经系统相关的胚胎中胚层和神经嵴衍生细胞中表达。这些数据表明，在妊娠中期，Evi1在一般细胞增殖、血管生成和细胞特异性发育信号传导中具有重要作用。
