A new conditional mouse mutant reveals specific expression and functions of connexin36 in neurons and pancreatic beta-cells.
A new conditional mouse mutant reveals specific expression and functions of connexin36 in neurons and pancreatic beta-cells.
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一种新的条件小鼠突变体揭示了神经元和胰腺β细胞中连接蛋白36的特定表达和功能。
DOI：
10.1016/j.yexcr.2007.12.024
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发表时间：
2008
影响因子：
3.7
通讯作者：
Wellershaus K
中科院分区：
文献类型：
--
作者：
Wellershaus K
连接蛋白36（Cx 36）是在中枢神经系统（CNS）的神经元和胰腺β-细胞中表达的主要连接蛋白同种型，即两种类型的可兴奋细胞，尽管它们的起源不同，但它们共享许多共同特征。先前对Cx 36缺陷小鼠的研究已经证明，Cx 36的缺失导致CNS和胰腺的表型异常，然而，由于所用动物模型的一般缺失性质，这不能归因于特定的细胞类型。迄今为止，使用由Cre/loxP策略产生的细胞类型特异性缺失来解决该限制的尝试由于缺乏来自floxed等位基因的Cx 36表达而变得复杂。我们现在已经产生了一个条件Cx 36缺陷的小鼠突变体，其中Cx 36的编码区两侧是loxP位点，随后是青色荧光蛋白（CFP）报告基因。在这里，我们发现Cx 36仍然在神经元和胰腺β细胞中从floxed等位基因表达。在这些细胞中，相对于野生型等位基因的表达水平，这种蛋白质的30-60%的降低并没有显著地干扰细胞偶联。Cx 36的删除无处不在和细胞类型特异性表达的Cre重组酶显示，CFP作为一个可靠的报告Cx 36在脑神经元中的表达，并在一定程度上在视网膜神经元，但不是在胰腺。在转录和蛋白质水平上记录了Cre介导的重组导致的Cx 36丢失。内分泌胰腺中Cx 36的细胞类型特异性缺失揭示了基础以及葡萄糖诱导的胰岛素分泌的重大改变，因此特别归因于胰腺Cx 36在β细胞功能控制中的重要调节作用。通过合适的Cre重组酶在CNS中Cx 36的细胞类型特异性缺失也应该有助于阐明Cx 36在不同神经元亚型中的功能作用。
Connexin36 (Cx36) is the main connexin isoform expressed in neurons of the central nervous system (CNS) and in pancreatic β-cells, i.e. two types of excitable cells that share – in spite of their different origins – a number of common features. Previous studies on Cx36 deficient mice have documented that loss of Cx36 resulted in phenotypic abnormalities in both the CNS and the pancreas which, however, could not be attributed to specific cell types due to the general deletion nature of the animal model used. Attempts to address this limitation using cell type specific deletions generated by the Cre/loxP strategy have so far been complicated by the lack of Cx36 expression from the floxed allele. We have now generated a conditional Cx36 deficient mouse mutant in which the coding region of Cx36 is flanked by loxP sites, followed by a cyan fluorescent protein (CFP) reporter gene. Here we show that Cx36 was still expressed from the floxed allele in neurons and pancreatic β-cells. In these cells, a 30–60% decrease of this protein, relative to the expression level of the wildtype allele, did not significantly perturb cell coupling. The deletion of Cx36 by ubiquitously and cell type specifically expressed Cre recombinases revealed that CFP functions as a reliable reporter for Cx36 expression in brain neurons and to some extent in retina neurons, but not in pancreas. Loss of Cx36 by Cre-mediated recombination was documented at transcript and protein levels. Cell type specific deletion of Cx36 in the endocrine pancreas revealed major alterations in the basal as well as the glucose-induced insulin secretion, hence specifically attributing to pancreatic Cx36 an important regulatory role in the control of β-cell function. Cell type specific deletion of Cx36 in the CNS by suitable Cre recombinases should also help to elucidate the functional role of Cx36 in different neuronal subtypes.
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小鼠连接蛋白编码 DNA 的一般或细胞类型特异性删除和替换。
影响因子：
4.8
作者：
M. Theis;T. M. Magin;A. Plum;Klaus Willecke
通讯作者：
Klaus Willecke
用 lacZ 报告基因一般和有条件地替换 Connexin43 编码 DNA，用于细胞自主表达分析
影响因子：
--
作者：
M. Theis;C. Mas;Britta Döring;O. Krüger;P. Herrera;P. Meda;K. Willecke
通讯作者：
K. Willecke
神经递质通过视网膜间隙连接耦合
DOI：
10.1523/jneurosci.18-24-10594.1998
发表时间：
1998
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
D. I. Vaney;J. Charles Nelson;D. Pow
通讯作者：
D. Pow
影响因子：
3.4
作者：
Weber, P;Metzger, D;Chambon, P
通讯作者：
Chambon, P
影响因子：
3.7
作者：
BOSCO, D;ORCI, L;MEDA, P
通讯作者：
MEDA, P