Ahnak/Desmoyokin is dispensable for proliferation, differentiation and maintenance of integrity in mouse epidermis
Ahnak/Desmoyokin is dispensable for proliferation, differentiation and maintenance of integrity in mouse epidermis
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DOI：
10.1111/j.0022-202x.2004.23412.x
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发表时间：
2004-10-01
影响因子：
6.5
通讯作者：
Hashimoto, T
中科院分区：
文献类型：
--
作者：
Kouno, M;Kondoh, G;Hashimoto, T
桥粒连接蛋白最早从牛鼻口表皮中分离得到，被认为是一种表皮桥粒相关蛋白。我们以前证明，Desmoyokin基因是相同的Ahnak基因，这是普遍表达和下调成神经细胞瘤。人们认为Ahnak/Desmoyokin与表皮细胞粘附、肿瘤发生、细胞增殖和分化以及胚胎发育有关。为了确定Ahnak/Desmoyokin的精确生物学功能，我们在ES细胞和小鼠中产生了无效突变。所得到的Ahnak/Desmoyokin缺陷的ES细胞正常分化为胚状体和神经细胞。突变小鼠存活且可生育，未显示出明显的发育缺陷。皮肤切片的电子显微镜检查表明，突变小鼠的表皮细胞间连接（包括桥粒）的超微结构与野生型小鼠没有区别。两阶段化学皮肤致癌实验表明，野生型和突变小鼠之间的皮肤肿瘤形成的频率或发病率没有差异。此外，在突变小鼠的其他组织和器官中未观察到肿瘤发生，直至2岁。这些结果使我们得出结论，Ahnak/Desmoyokin缺乏对表皮细胞粘附，肿瘤发生，细胞增殖和分化以及整体小鼠发育的影响很小。
Desmoyokin was first isolated from bovine muzzle epidermis and thought to be an epidermal desmosome-related protein. We previously demonstrated that the Desmoyokin gene is identical to the Ahnak gene, which is expressed ubiquitously and downregulated in neuroblastomas. It was assumed Ahnak/Desmoyokin was associated with epidermal cell adhesion, tumorigenesis, cell proliferation and differentiation, and embryonic development. To determine the precise biological function of Ahnak/Desmoyokin, we generated a null mutation in ES cells and mice. The resultant Ahnak/Desmoyokin-deficient ES cells normally differentiated into embryoid bodies and neural cells. The mutant mice were viable and fertile and showed no gross developmental defects. Electron microscopic examination of skin sections demonstrated that the ultrastructure of epidermal intercellular junctions, including desmosomes, of the mutant mice was indistinguishable from that of wild-type mice. Two-stage chemical skin carcinogenesis experiments showed no difference in frequency or onset of cutaneous tumor formation between wild-type and mutant mice. Moreover, no tumorigenesis was observed in other tissues and organs of mutant mice up to 2 y of age. These results lead us to conclude that Ahnak/Desmoyokin deficiency has only a minimal effect on epidermal cell adhesion, tumorigenesis, cell proliferation and differentiation, and overall mouse development.