Peripheral lymphangiogenesis in mice depends on ectodermal connexin-26 (Gjb2)
Peripheral lymphangiogenesis in mice depends on ectodermal connexin-26 (Gjb2)
复制标题
DOI：
10.1242/jcs.084186
复制
发表时间：
2011-08-15
影响因子：
4
通讯作者：
Willecke, Klaus
中科院分区：
文献类型：
--
作者：
Dicke, Nikolai;Pielensticker, Nicole;Willecke, Klaus
为了研究 connexin-26（Cx26，也称为间隙连接 beta-2 蛋白；Gjb2）的特定功能，我们生成了表达 floxed lacZ 报告基因或在 Cre 介导的删除后表达 connexin-32 (Cx32) 编码 DNA 的敲入小鼠，两者均由内源性 Cx26 启动子驱动。杂合 Cx26knock-inCx32 (Cx26KICx32) 胚胎正常发育直至胚胎第 14.5 天，但在出生前因严重淋巴水肿而死亡。尽管颈静脉淋巴囊发育正常，但这些胚胎的真皮毛细淋巴管网络严重减少。通过分析 β-半乳糖苷酶报告蛋白表达和淋巴管或血液内皮特异性标记蛋白，我们证明 Cx26 表达在时间上与淋巴管生成密切相关。当分别使用 Prx1-Cre 或 Tie2-Cre 小鼠品系将 Cre 介导的重组定向至间充质或血液内皮时，在 Cx26KICx32 小鼠中没有观察到明显的表型异常。相比之下，角蛋白-5-Cre介导的Cx26替换为Cx32或删除两个Cx26等位基因显示出与一般Cx26KICx32表型相似的严重淋巴水肿。因此，外胚层中 Cx26 的有条件消融（功能丧失）会导致毛细淋巴管部分破坏和胚胎死亡。我们得出的结论是，小鼠真皮淋巴管的适当发育取决于外胚层中 Cx26 的表达。
In order to study the specific function of connexin-26 (Cx26, also known as gap junction beta-2 protein; Gjb2), we generated knockin mice that expressed either a floxed lacZ reporter or, after Cre-mediated deletion, connexin-32 (Cx32)-coding DNA, both driven by the endogenous Cx26 promoter. Heterozygous Cx26knock-inCx32 (Cx26KICx32) embryos developed normally until embryonic day 14.5 but died before birth with severe lymphedemas. Although the jugular lymph sacs were normally developed, these embryos had a strongly reduced dermal lymphatic capillary network. By analyses of beta-galactosidase reporter protein expression and lymphatic or blood endothelial-specific marker proteins, we demonstrated that Cx26 expression is temporally closely linked to lymphangiogenesis. No obvious phenotypic abnormalities were observed in Cx26KICx32 mice when Cre-mediated recombination was directed to mesenchyme or blood endothelium using the Prx1-Cre or Tie2-Cre mouse strains, respectively. By contrast, keratin-5-Cre-mediated replacement of Cx26 with Cx32 or deletion of both Cx26 alleles revealed severe lymphedemas similar to the general Cx26KICx32 phenotype. Thus, conditional ablation of Cx26 (loss of function) in ectoderm leads to partial disruption of lymphatic capillaries and embryonic death. We conclude that appropriate development of dermal lymphatic vessels in mice is dependent on the expression of Cx26 in the ectoderm.