Loss of connexin 26 in mammary epithelium during early but not during late pregnancy results in unscheduled apoptosis and impaired development
Loss of connexin 26 in mammary epithelium during early but not during late pregnancy results in unscheduled apoptosis and impaired development
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DOI：
10.1016/j.ydbio.2003.11.022
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发表时间：
2004-03-15
影响因子：
2.7
通讯作者：
Hennighausen, L
中科院分区：
文献类型：
--
作者：
Bry, C;Maass, K;Hennighausen, L
缝隙连接是由连接蛋白家族（Cxs）形成的细胞间通道。在乳腺组织中，Cx 26和Cx 32存在于分泌上皮中，Cx43定位于肌上皮中。Cx 26和Cx 32的表达分别在妊娠和哺乳期间被诱导，从而表明它们在腺体的功能发育中具有独特的作用。使用几种遗传改变的小鼠品系探索了对这些连接蛋白的需求：具有失活Cx 32基因的小鼠、Cx43基因被Cx 32基因取代的小鼠（Cx43 KI 32小鼠）和Cx 26基因在不同发育阶段使用Cre-loxP重组在乳腺上皮中特异性消融的小鼠。在Cx 32缺失小鼠和Cx43 KI 32乳腺组织中获得了正常的乳腺发育。相反，青春期前乳腺上皮细胞中Cx 26的缺失导致妊娠期间小叶-肺泡发育和细胞死亡增加，并伴有泌乳受损。在妊娠后期乳腺上皮细胞中Cx 26的缺失不会对功能性乳腺发育产生不利影响。这些结果表明，Cx 26的存在是至关重要的，在早期阶段，但不是在妊娠结束时，组织已完成功能分化。Cx 26被认为是一种肿瘤抑制基因，在5次妊娠后对Cx 26缺失的乳腺组织进行了评价。未观察到过度增殖或增生，表明Cx 26不起肿瘤抑制剂的作用。爱思唯尔公司出版
Gap junctions are intercellular channels that are formed by the protein family of connexins (Cxs). In mammary tissue, Cx26 and Cx32 are present in the secretory epithelium and Cx43 is localized in the myoepithelium. The expression of Cx26 and Cx32 is induced during pregnancy and lactation, respectively, thus suggesting unique roles for them in the functional development of the gland. The requirement for these connexins was explored using several strains of genetically altered mice: mice with an inactivated Cx32 gene, mice in which the Cx43 gene had been replaced with the Cx32 gene (Cx43KI32 mice) and mice in which the Cx26 gene was specifically ablated in mammary epithelium at different stages of development using Cre-loxP-based recombination. Normal mammary development was obtained in Cx32-null mice and in Cx43KI32 mammary tissue. In contrast, loss of Cx26 in mammary epithelium before puberty resulted in abrogated lobulo-alveolar development and increased cell death during pregnancy, which was accompanied by impaired lactation. Loss of Cx26 in mammary epithelium during the later part of pregnancy did not adversely interfere with functional mammary development. These results demonstrate that the presence of Cx26 is critical during early stages but not during the end of pregnancy when the tissue has completed functional differentiation. Cx26 is considered a tumor suppressor gene and Cx26-null mammary tissue was evaluated after five pregnancies. No hyperproliferation or hyperplasia was observed, suggesting that Cx26 does not function as a tumor suppressor. Published by Elsevier Inc.