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Generation and Phenotypic Analysis of the IL-10RAR104W/R104W Mouse Model
Xiaoya Cao1,2, Zhiyang Zeng3,4,2, Xiya Cao4
1Department of General Surgery, South Campus of Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 201499, China.
Inflammatory Bowel Diseases
|September 29, 2025
Summary
A new mouse model with IL-10RA mutations develops colitis, offering insights into very-early-onset inflammatory bowel disease (VEO-IBD) and potential therapeutic strategies.
Area of Science:
- Immunology
- Gastroenterology
- Genetics
Background:
- Very-early-onset inflammatory bowel disease (VEO-IBD) affects young children, often linked to IL-10 receptor alpha (IL-10RA) mutations.
- The exact causes of VEO-IBD are unclear, and treatment options are limited, necessitating better research models.
Purpose of the Study:
- To create and characterize a humanized mouse model for VEO-IBD research.
- To investigate the pathogenesis of VEO-IBD using a novel mouse model.
Main Methods:
- Generated a mouse model with a specific IL-10RA mutation using CRISPR/Cas9 technology.
- Assessed colitis phenotype, immune cell infiltration, cytokine levels, and macrophage populations in the mutant mice.
Main Results:
- The mouse model developed spontaneous colitis with abnormal colonic structure and immune cell infiltration.
- Mutant mice showed altered inflammatory cytokine levels, increased pro-inflammatory macrophages, and reduced anti-inflammatory macrophages.
- Bone marrow transplantation modulated macrophage populations and reduced intestinal inflammation; tumor growth was accelerated in mutant mice.
Conclusions:
- Successfully developed a humanized mouse model exhibiting stable spontaneous colitis.
- This model is valuable for exploring VEO-IBD therapies and understanding disease mechanisms.
