Department of Animal Sciences, Purdue University, West Lafayette, Indiana, United States of America.
PLoS One. 2013;8(1):e53781. doi: 10.1371/journal.pone.0053781. Epub 2013 Jan 21.
Intestinal mucin 2 (MUC2) encodes a heavily glycosylated, gel-forming mucin, which creates an important protective mucosal layer along the gastrointestinal tract in humans and other species. This first line of defense guards against attacks from microorganisms and is integral to the innate immune system. As a first step towards characterizing the innate immune response of MUC2 in different species, we report the cloning of a full-length, 11,359 bp chicken MUC2 cDNA, and describe the genomic organization and functional annotation of this complex, 74.5 kb locus. MUC2 contains 64 exons and demonstrates distinct spatiotemporal expression profiles throughout development in the gastrointestinal tract; expression increases with gestational age and from anterior to posterior along the gut. The chicken protein has a similar domain organization as the human orthologue, with a signal peptide and several von Willebrand domains in the N-terminus and the characteristic cystine knot at the C-terminus. The PTS domain of the chicken MUC2 protein spans ∼1600 amino acids and is interspersed with four CysD motifs. However, the PTS domain in the chicken diverges significantly from the human orthologue; although the chicken domain is shorter, the repetitive unit is 69 amino acids in length, which is three times longer than the human. The amino acid composition shows very little similarity to the human motif, which potentially contributes to differences in the innate immune response between species, as glycosylation across this rapidly evolving domain provides much of the musical barrier. Future studies of the function of MUC2 in the innate immune response system in chicken could provide an important model organism to increase our understanding of the biological significance of MUC2 in host defense and highlight the potential of the chicken for creating new immune-based therapies.
肠黏蛋白 2（MUC2）编码一种高度糖基化、形成凝胶的黏蛋白，在人类和其他物种的胃肠道中形成重要的保护性黏膜层。这种第一道防线可以抵御微生物的攻击，是先天免疫系统的重要组成部分。为了初步阐明不同物种中 MUC2 的先天免疫反应，我们克隆了全长 11359bp 的鸡 MUC2 cDNA，并描述了这个复杂的 74.5kb 基因座的基因组组织和功能注释。MUC2 包含 64 个外显子，在胃肠道的发育过程中表现出明显的时空表达模式；其表达随着胎龄的增加以及从肠道的前到后逐渐增加。鸡蛋白与人类同源物具有相似的结构域组织，在 N 端具有信号肽和几个 von Willebrand 结构域，在 C 端具有特征性的半胱氨酸结。鸡 MUC2 蛋白的 PTS 结构域跨越约 1600 个氨基酸，其中散布着四个 CysD 基序。然而，鸡的 PTS 结构域与人类同源物有很大的不同；尽管鸡的结构域较短，但重复单元的长度为 69 个氨基酸，是人类的三倍长。该氨基酸组成与人类基序非常相似，这可能导致不同物种之间先天免疫反应的差异，因为在这个快速进化的结构域中，糖基化提供了大部分的音乐屏障。未来对鸡先天免疫反应系统中 MUC2 功能的研究可能为我们提供一个重要的模式生物，以增加我们对 MUC2 在宿主防御中的生物学意义的理解，并强调鸡在创造新的免疫治疗方法方面的潜力。
