Maxeiner Stephan, Dedek Karin, Janssen-Bienhold Ulrike, Ammermüller Josef, Brune Hendrik, Kirsch Taryn, Pieper Mario, Degen Joachim, Krüger Olaf, Willecke Klaus, Weiler Reto
Institute for Genetics, Division of Molecular Genetics, University of Bonn, 53117 Bonn, Germany.
J Neurosci. 2005 Jan 19;25(3):566-76. doi: 10.1523/JNEUROSCI.3232-04.2005.
Connexin45 (Cx45) is known to be expressed in the retina, but its functional analysis was problematic because general deletion of Cx45 coding DNA resulted in cardiovascular defects and embryonic lethality at embryonic day 10.5. We generated mice with neuron-directed deletion of Cx45 and concomitant activation of the enhanced green fluorescent protein (EGFP). EGFP labeling was observed in bipolar, amacrine, and ganglion cell populations. Intracellular microinjection of fluorescent dyes in EGFP-labeled somata combined with immunohistological markers revealed Cx45 expression in both ON and OFF cone bipolar cells. The scotopic electroretinogram of mutant mice revealed a normal a-wave but a 40% reduction in the b-wave amplitude, similar to that found in Cx36-deficient animals, suggesting a possible defect in the rod pathway of visual transmission. Indeed, neurotransmitter coupling between AII amacrine cells and Cx45-expressing cone bipolar cells was disrupted in Cx45-deficient mice. These data suggest that both Cx45 and Cx36 participate in the formation of functional heterotypic electrical synapses between these two types of retinal neurons that make up the major rod pathway.
已知连接蛋白45（Cx45）在视网膜中表达，但其功能分析存在问题，因为Cx45编码DNA的整体缺失会导致心血管缺陷以及在胚胎第10.5天出现胚胎致死性。我们构建了神经元定向缺失Cx45并同时激活增强型绿色荧光蛋白（EGFP）的小鼠。在双极细胞、无长突细胞和神经节细胞群体中观察到了EGFP标记。在EGFP标记的胞体中进行荧光染料的细胞内微注射并结合免疫组织学标记，结果显示在ON型和OFF型视锥双极细胞中均有Cx45表达。突变小鼠的暗视视网膜电图显示a波正常，但b波振幅降低了40%，这与Cx36缺陷动物中的情况相似，提示视觉传导的视杆通路可能存在缺陷。实际上，在Cx45缺陷小鼠中，AII无长突细胞与表达Cx45的视锥双极细胞之间的神经递质偶联被破坏。这些数据表明，Cx45和Cx36都参与了构成主要视杆通路的这两种视网膜神经元之间功能性异型电突触的形成。
