Deletion of connexin45 in mouse retinal neurons disrupts the rod/cone signaling pathway between AII amacrine and ON cone bipolar cells and leads to impaired visual transmission
Deletion of connexin45 in mouse retinal neurons disrupts the rod/cone signaling pathway between AII amacrine and ON cone bipolar cells and leads to impaired visual transmission
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DOI：
10.1523/jneurosci.3232-04.2005
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发表时间：
2005-01-19
影响因子：
5.3
通讯作者：
Weiler, R
中科院分区：
文献类型：
--
作者：
Maxeiner, S;Dedek, K;Weiler, R
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，因为编码Cx45的DNA的普遍缺失会导致心血管缺陷和胚胎在第10.5天死亡。我们产生了神经元定向缺失Cx45并伴随着增强型绿色荧光蛋白(EGFP)激活的小鼠。在双极细胞、无长突细胞和神经节细胞群中观察到了EGFP标记。在EGFP标记的胞体内显微注射荧光染料结合免疫组织学标记，发现Cx45在锥体上和锥体外双极细胞中都有表达。突变小鼠的暗视视网膜电信号显示a波正常，但b波幅度降低40%，与Cx36基因缺陷的动物相似，表明视觉传递的杆状通路可能存在缺陷。事实上，在Cx45基因缺陷的小鼠中，AII无长突细胞和表达Cx45的锥体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。
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.