Cloning, Annotation and Developmental Expression of the Chicken Intestinal MUC2 Gene

Abstract

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.

Susceptibility of Broiler Chickens to Coccidiosis When Fed Subclinical Doses of Deoxynivalenol and Fumonisins—Special Emphasis on the Immunological Response and the Mycotoxin Interaction

“…Another gene indirectly related to inflammation is MUC2, the most abundant mucin in the intestine. The low expression of MUC2 observed in the present study is believed to also contribute to inflammation as its deficiency has been reported to increase bacterial translocation and inflammation [38]. In line with MUC2 expression, the very dry aspect of feces suggested that the mucus was severely compromised and could not play its role as a layer of protection in the intestine.…”

Protected Blend of Organic Acids and Essential Oils Improves Growth Performance, Nutrient Digestibility, and Intestinal Health of Broiler Chickens Undergoing an Intestinal Challenge

“…Besides tight junction proteins, mucins produced by Goblet cells form the first line of defense in maintaining intestinal barrier (57). Mucin-2 is the main mucin produced and is considered a biomarker of intestinal health because it avoids microbial adhesion to the mucosa (58,59). In the present study, broilers on challenged control group had the MUC2 expression downregulated compared to broilers on non-challenged and P(OA+EO) groups.…”

Identification of Potential Biomarkers for Gut Barrier Failure in Broiler Chickens

“…Evolutionary studies suggest that mucins share a common ancestor, since their domain structures are well conserved in metazoans ( 71 , 81 ). All mucins (MUC) contain at least one PTS domain, a region rich in proline, threonine, and serine ( 18 , 82 ). Chicken MUC2 has been reported to be remarkably similar to human and mouse outside of the central PTS domain, but is highly divergent within this central repetitive structure ( 82 , 83 ).…”