Analysis of LGR4 receptor distribution in human and mouse tissues.
Analysis of LGR4 receptor distribution in human and mouse tissues.
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DOI：
10.1371/journal.pone.0078144
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Yi J;Xiong W;Gong X;Bellister S;Ellis LM;Liu Q
LGR4是一种R-响应蛋白受体，对Wnt信号有很强的正向作用。它在发育中起着关键作用，因为它在小鼠身上的消融导致了胚胎/新生儿的完全死亡，并在多个器官中出现了严重的缺陷。人类LGR4单倍型缺陷与几种疾病相关，包括皮肤鳞状细胞癌风险增加、出生体重减轻、电解质失衡和睾酮水平降低，这些与LGR4基因缺陷小鼠的表型相似。使用基因捕获报告酶等位基因，广泛分析了LGR4在小鼠体内的组织分布。然而，它在人体组织中的表达模式在很大程度上仍不清楚。我们已经开发了LGR4特异性的单抗，并用它们通过免疫组织化学分析检测了LGR4在选定的成人、人和小鼠组织中的表达。在皮肤的表皮和毛囊、胰岛细胞以及雄性和雌性生殖器官的上皮细胞中均观察到强烈的LGR4样免疫反应。尤其令人感兴趣的是，LGR4在生殖细胞和胰岛细胞中高度表达，这两种细胞具有重要的意义，因为R-Respondin-LGR4信号在成体干细胞存活中扮演着重要角色。此外，大多数结肠肿瘤的LGR4受体水平升高。总体而言，通过该IHC分析定位的LGR4在人类组织中的表达模式与从基因陷阱等位基因中揭示的在小鼠中的表达模式相似。重要的是，这种模式有力地支持了LGR4在皮肤、肾脏、生殖系统和其他器官的发育和维护中的重要作用。
LGR4 is an R-spondin receptor with strong positive effect on Wnt signaling. It plays a critical role in development as its ablation in the mouse led to total embryonic/neonatal lethality with profound defects in multiple organs. Haplotype insufficiency of LGR4 in human was associated with several diseases, including increased risk of squamous cell carcinoma of the skin, reduced birth weights, electrolyte imbalance, and decreased levels of testosterone, which are similar to the phenotypes of LGR4-hypomorphic mice. Tissue distribution of LGR4 was extensively analyzed in the mouse using gene-trap reporter enzyme alleles. However, its expression pattern in human tissues remained largely unknown. We have developed LGR4-specific monoclonal antibodies and used them to examine the expression of LGR4 in selected adult human and mouse tissues by immunohistochemical analysis. Intense LGR4-like immunoreactivity was observed in the epidermis and hair follicle of the skin, pancreatic islet cells, and epithelial cells in both the male and female reproductive organs. Of particular interest is that LGR4 is highly expressed in germ cells and pancreatic islet cells, which have important implications given the role of R-spondin-LGR4 signaling in the survival of adult stem cells. In addition, the majority of colon tumors showed elevated levels of LGR4 receptor. Overall, the expression pattern of LGR4 in human tissues mapped by this IHC analysis is similar to that in the mouse as revealed from gene trap alleles. Importantly, the pattern lends strong support to the important role of LGR4 in the development and maintenance of skin, kidney, reproductive systems, and other organs.
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影响因子：
--
作者：
Kato, Shigeki;Matsubara, Mitsunobu;Nishimori, Katsuhiko
通讯作者：
Nishimori, Katsuhiko
影响因子：
64.8
作者：
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通讯作者：
de Sauvage, Frederic J.
影响因子：
7.7
作者：
Mustata, Roxana C.;Van Loy, Tom;Garcia, Marie-Isabelle
通讯作者：
Garcia, Marie-Isabelle
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影响因子：
4.8
作者：
Liu, Shijie;Qian, Yu;Li, Dali
通讯作者：
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影响因子：
--
作者：
Mazerbourg, S;Bouley, DM;Hsueh, AJW
通讯作者：
Hsueh, AJW