ArticleOncogene2016
Mice deficient in Muc4 are resistant to experimental colitis and colitis-associated colorectal cancer.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- Clinical Significance of Mucin Signatures in Inflammatory Bowel Diseases: A Systematic Review of Their Expression Patterns, Polymorphisms, and Post-translational Modifications.Inflammatory bowel diseases · 2026Pooled it
- MUC4 O-GlcNAcylation Regulates the Epithelial Phenotype in Conjunctival Epithelial Cells.Biochemical genetics · 2025Article
- Effect of Anti-TNF Monoclonal Antibody on Enteric Neurons and Enteric Glial Cells in Experimental Colitis.Digestive diseases and sciences · 2025Article
- The Intestinal Mucin Isoform Landscape Reveals Region-Specific Biomarker Panels for Inflammatory Bowel Disease Patient Stratification.Journal of Crohn's & colitis · 2025Article
- Digital spatial profiling identifies molecular changes involved in development of colitis-associated colorectal cancer.Frontiers in oncology · 2024Article
- Article
- Red Cabbage Juice-Mediated Gut Microbiota Modulation Improves Intestinal Epithelial Homeostasis and Ameliorates Colitis.International journal of molecular sciences · 2023Article
- Article
- Roles unveiled for membrane-associated mucins at the ocular surface using a Muc4 knockout mouse model.Scientific reports · 2023Article
- Elucidation of the genetic causes of bicuspid aortic valve disease.Cardiovascular research · 2023Article
- Review
- Discovery of indole analogues fromFrontiers in pharmacology · 2023Article
- Mucosal DNA methylome alteration in Crohn's disease: surgical and non-surgical groups.Frontiers in genetics · 2023Article
- Differential analysis of intestinal microbiota and metabolites in mice with dextran sulfate sodium-induced colitis.World journal of gastroenterology · 2022Article
- Anti-mucin 4 fluorescent antibody brightly targets colon cancer in patient-derived orthotopic xenograft mouse models: A proof-of-concept study for future clinical applications.American journal of surgery · 2022Article
- Rab11FIP1-deficient mice develop spontaneous inflammation and show increased susceptibility to colon damage.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Mucin 16 Promotes Colorectal Cancer Development and Progression Through Activation of Janus Kinase 2.Digestive diseases and sciences · 2022Article
- Chemically Induced Colitis-Associated Cancer Models in Rodents for Pharmacological Modulation: A Systematic Review.Journal of clinical medicine · 2022Review
- Decreased Tissue Omega-6/Omega-3 Fatty Acid Ratio Prevents Chemotherapy-Induced Gastrointestinal Toxicity Associated with Alterations of Gut Microbiome.International journal of molecular sciences · 2022Article
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
MUC4, a large transmembrane mucin normally expressed in the small and large intestine, is differentially expressed during inflammatory and malignant conditions of the colon. However, the expression pattern and the role of MUC4 in colitis and colorectal cancer (CRC) are inconclusive. Therefore, the aim of this study was to understand the role of Muc4 during inflammatory and malignant conditions of the colon. Here, we generated Muc4(-/-) mice and addressed its role in colitis and colitis-associated CRC using dextran sodium sulfate (DSS) and azoxymethane (AOM)-DSS experimental models, respectively. Muc4(-/-) mice were viable, fertile with no apparent defects. Muc4(-/-) mice displayed increased resistance to DSS-induced colitis compared with wild-type (WT) littermates that was evaluated by survival rate, body weight loss, diarrhea and fecal blood score, and histological score. Reduced infiltration of inflammatory cells, that is, CD3(+) lymphocytes and F4/80(+) macrophages was observed in the inflamed mucosa along with reduction in the mRNA levels of inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α and anti-microbial genes Lysozyme M and SLPI in the colon of Muc4(-/-) mice compared with WT littermates. Compensatory upregulation of Muc2 and Muc3 mucins under basal and DSS treatment conditions partly explains the resistance observed in Muc4(-/-) mice. Accordingly, Muc4(-/-) mice exhibited significantly reduced tumor burden compared with WT mice assessed in a colitis-induced tumor model using AOM/DSS. An increased percentage of Ki67(+) nuclei was observed in the tumors from WT compared with Muc4(-/-) mice suggesting Muc4 to be critical in intestinal cell proliferation during tumorigenesis. Taken together, we conclusively demonstrate for the first time the role of Muc4 in driving intestinal inflammation and inflammation-associated tumorigenesis using a novel Muc4(-/-) mouse model.
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