First mouse model of celiac disease is developed

February 19, 2020

By Amy Ratner, Medical and Science News Analyst

The first mouse model with the same gene and immune system as people who have celiac disease has been developed by researchers at the University of Chicago Celiac  Disease Center.

The scientific breakthrough has been in the making for two decades, according to a story published by the university’s UChicago news.

The mouse model “provides a vital tool for developing and testing new treatments for [celiac] disease,” the story says. Details of how the model was developed were published in the journal Nature.

It’s the first model where mice develop damage to the small intestine just by eating gluten, which can later reverse itself on a gluten-free diet, senior study author Bana Jabri, MD, director of the celiac center told UChicago news.

One of the key characteristics of the mouse model is that is the first to have HLA-DQ8, one of the genes associated with development of celiac disease in humans. The mouse model develops damage to the lining of the small intestine when exposed to gluten. When gluten is removed through gluten-free diet, the intestine can recover and heal just as it does when a person has celiac disease.

Mouse models are special strains of mice use to study human disease and how to prevent and treat it. Mice share genetic and physiological similarities with humans and naturally develop cancer, hypertension, diabetes, osteoporosis and glaucoma. In addition, certain diseases that afflict humans but normally do not strike mice, such as cystic fibrosis and Alzheimer’s, can be induced by manipulating the mouse genome and environment, according to the National Human Genome Research Institute.

Genes alone are not enough to cause the development of celiac disease and many in the general population have HLA-Q8 or HLA-DQ2, which is also associated with celiac disease. Studies using the mouse model could uncover general principles for treatments that would apply to patients with either gene, including research exploring making gluten tolerable to those with celiac disease and investigation of vaccines, said Valerie Abadie, PhD, lead study author.  But treatments designed specifically to block gluten from binding to HLA-DQ2 cannot be tested with the mouse model.

Based on studies of celiac disease patients, Jabri and colleagues have that proposed high levels of IL-15, an inflammatory protein, in the lining of the small intestine also needs to be present for intestinal damage to occur. This damage, detected through a biopsy, is the gold standard for diagnosis of celiac disease. Environmental and other factors are also thought to pay a role in the development of celiac disease.

“By reflecting the complex interaction between gluten, genetics and IL-15-driven tissue inflammation, this mouse model provides the opportunity to both increase our understanding of coeliac disease, and develop new therapeutic strategies,” wrote authors of the mouse model study.

Researchers have studied celiac disease in patients to understand the nature of the disease, Jabri told UChicago news. She said scientists can now use the mouse model to identify new targets for drugs and test them “in a model that faithfully represents the condition in humans. Jabri called the mouse model “a vital tool for developing new treatments to reverse celiac [disease] once it has developed – or prevent it from developing in people at risk for the disease.”

You can read more details about the mouse model study here and here.

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