Xiang M, Zhou L, Nathans J
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Vis Neurosci. 1996 Sep-Oct;13(5):955-62. doi: 10.1017/s0952523800009184.
Brn-3a, Brn-3b, and Brn-3c are highly homologous POU-domain transcription factors that are expressed in subsets of retinal ganglion cells. From each of the mouse Brn-3 genes, a DNA segment ranging in size from 4.6 to 13.4 kb and located immediately upstream of the start site of translation was joined to a human placental alkaline phosphatase (AP) reporter cDNA. Following the introduction of each construct into the mouse germline, a total of 19 transgenic lines were obtained, of which 16 expressed the AP reporter in the retina. Unexpectedly, at least 14 of the 16 expressing lines showed AP activity in subsets of amacrine cells, and these subsets typically differed among mouse lines injected with the same construct. Transgene expression was also found in ganglion cells in four lines and bipolar cells in seven lines. In all cases AP activity was confined to cells in the inner nuclear layer and the ganglion cell layer. The expression of Brn-3 transgenes in multiple cell types in the inner retina is reminiscent of earlier experiments in which visual pigment transgenes were found to be expressed in multiple cell types in the outer retina. Taken together, these observations suggest that anatomically and/or functionally related retinal neurons contain partially overlapping transcriptional regulatory specificities.
Brn-3a、Brn-3b和Brn-3c是高度同源的POU结构域转录因子,在视网膜神经节细胞亚群中表达。从小鼠的每个Brn-3基因中,将一个大小在4.6至13.4 kb之间、位于翻译起始位点上游紧邻处的DNA片段与一个人胎盘碱性磷酸酶(AP)报告基因cDNA连接。将每个构建体导入小鼠种系后,共获得了19个转基因品系,其中16个在视网膜中表达AP报告基因。出乎意料的是,16个表达品系中至少有14个在无长突细胞亚群中显示出AP活性,并且这些亚群在注射相同构建体的小鼠品系之间通常有所不同。在4个品系的神经节细胞和7个品系的双极细胞中也发现了转基因表达。在所有情况下,AP活性都局限于内核层和神经节细胞层中的细胞。Brn-3转基因在内视网膜的多种细胞类型中的表达让人想起早期的实验,在这些实验中发现视觉色素转基因在外视网膜的多种细胞类型中表达。综上所述,这些观察结果表明,在解剖学和/或功能上相关的视网膜神经元含有部分重叠的转录调控特异性。