Related Experiment Video
Updated: May 29, 2026
Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids
Published on: June 2, 2023
Colonic gene expression patterns of mucin Muc2 knockout mice reveal various phases in colitis development
Peng Lu1, Nanda Burger-van Paassen, Maria van der Sluis
1Laboratory of Pediatrics, Division Neonatology, Erasmus MC-Sophia, Rotterdam, The Netherlands.
Background:
Mucin Muc2 knockout (Muc2(-/-)) mice spontaneously develop colitis.
Methods:
To identify genes and biological responses which play a pivotal role during colitis development in Muc2(-/-) mice, gene expression profiles of colonic tissues from 2- and 4-week-old Muc2(-/-) and wildtype mice were determined using microarrays.
Results:
The majority of highly upregulated genes in 2-week-old as well as 4-week-old Muc2(-/-) mice were primarily involved in immune responses related to antigen processing/presentation, B-cell and T-cell receptor signaling, leukocyte transendothelial migration, and Jak-STAT signaling. Specifically, Muc2(-/-) mice expressed high levels of immunoglobulins, murine histocompatibility-2, proinflammatory cytokines, chemokines, and antimicrobial proteins. Additionally, in 4-week-old Muc2(-/-) mice, expression of genes involved in cell structure related pathways was significantly altered. Particularly, the tight junction-associated gene claudin-10 was upregulated, whereas claudin-1 and claudin-5 were downregulated. Furthermore, 4-week-old Muc2(-/-) mice showed increased expression of genes regulating cell growth in conjunction with increased crypt length and increased epithelial proliferation.
Conclusions:
Muc2-deficiency leads to an active inflammatory response in 2- and 4-week-old Muc2(-/-) mice as demonstrated by the altered expression in immune response related genes. In addition, 4-week-old Muc2(-/-) mice also showed a decrease in epithelial barrier function and an increase in epithelial proliferation as indicated by, respectively, the altered expression in tight junction-related genes and upregulation of genes stimulating cell growth. Remarkably, upregulation of genes stimulating cell growth correlated with increased crypt length and increased epithelial proliferation in 4-week-old Muc2(-/-) mice. Together, these data demonstrate that there are distinct phases in colitis development in 2-4-week-old Muc2(-/-) mice.
Insights
Mucin Muc2 knockout mice develop colitis due to immune responses and altered epithelial barrier function. These findings reveal distinct phases in colitis development in these mice.
Area of Science:
- Gastroenterology
- Immunology
- Molecular Biology
Background:
- Mucin Muc2 knockout (Muc2(-/-)) mice spontaneously develop colitis.
- Mucin 2 is crucial for maintaining intestinal barrier function.
Purpose of the Study:
- To identify key genes and biological responses during colitis development in Muc2(-/-) mice.
- To analyze gene expression profiles in colonic tissues at different stages of colitis.
Main Methods:
- Gene expression profiling using microarrays.
- Comparison of colonic tissues from 2- and 4-week-old Muc2(-/-) and wildtype mice.
Main Results:
- Upregulation of immune response genes (antigen processing, T/B-cell signaling, leukocyte migration, Jak-STAT signaling) in Muc2(-/-) mice.
- Altered expression of tight junction genes (claudin-10 upregulated, claudin-1/5 downregulated) and increased epithelial proliferation in 4-week-old Muc2(-/-) mice.
- High expression of immunoglobulins, MHC-2, cytokines, chemokines, and antimicrobial proteins observed.
Conclusions:
- Mucin 2 deficiency triggers active inflammation and distinct phases of colitis development.
- Impaired epithelial barrier function and increased proliferation occur in later stages of colitis in Muc2(-/-) mice.
- Gene expression changes highlight the roles of immune responses and epithelial dynamics in colitis pathogenesis.
