Mice with Abnormal Mucin Assembly Develop Inflammation Similar to Ulcerative Colitis
Author Information
Author(s): Heazlewood Chad K, Cook Matthew C, Eri Rajaraman, Price Gareth R, Tauro Sharyn B, Taupin Douglas, Thornton David J, Png Chin Wen, Crockford Tanya L, Cornall Richard J, Adams Rachel, Kato Masato, Nelms Keats A, Hong Nancy A, Florin Timothy H. J, Goodnow Christopher C, McGuckin Michael A
Primary Institution: Mater Medical Research Institute and the University of Queensland
Hypothesis
Can mutations in the Muc2 gene lead to inflammation resembling ulcerative colitis in mice?
Conclusion
The study suggests that mucin misfolding and endoplasmic reticulum stress may initiate colitis in mice, which could be relevant to human ulcerative colitis.
Supporting Evidence
- 100% of mice with mutations developed mild spontaneous intestinal inflammation by 6 weeks.
- 25% and 40% of the two strains developed severe clinical signs of colitis by age 1 year.
- Mutant mice showed increased production of inflammatory cytokines in the colon.
- Similar accumulation of MUC2 precursor was found in human ulcerative colitis.
- ER stress was evidenced by increased GRP78 expression in mutant mice.
- Histological analysis revealed goblet cell depletion and increased leukocyte infiltration.
Takeaway
Scientists made special mice with a gene change that caused their bodies to make mucus incorrectly, leading to gut problems like those seen in a disease called ulcerative colitis.
Methodology
The researchers used random mutagenesis to create two mouse models with mutations in the Muc2 gene and assessed their intestinal health over time.
Limitations
The study does not identify the genetic or environmental drivers of ER stress in human colitis.
Statistical Information
P-Value
p<0.01
Statistical Significance
p<0.01
Digital Object Identifier (DOI)
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