Forsøksdyr: Pilot study to establish intraduodenal administration of antigen and study antigen-specific B cell responses in the gut.

Godkjenningsdato 25.03.2020

Godkjenningsperiode 25.03.2020-25.03.2023

1 Purpose
Transglutaminase 2 (TG2) is thought to have a critical role in celiac disease, and the enzyme is also the target of disease-specific autoantibodies. The mechanisms, kinetics and location of TG2 activation, and how the antibody response to TG2 is induced, are not understood. In this project, we will establish gastrointestinal surgery to deliver TG2-proteins directly into the lumen of the small intestine (intraduodenal administration) in order to develop a mouse model that allows use to study the mechanisms behind anti-TG2 autoantibody formation in celiac disease.
2 Distress
We expect animals to experience moderate pain during the post-surgical recovery period following the laparotomy incisions.
3 Expected benefit
A better understanding is crucial for our understanding of celiac disease pathogenesis, and will enable the development of improved drugs that inhibit TG2 activity in patients.
4 Number of animals, and what kind
The application involves 291 animals, wild type C57Bl/6 mice to establish the technique and partly humanized mice specific for celiac disease related studies.
5 How to adhere to 3R
We will use both local and systemic analgesia during surgery and systemic analgesia during the post-surgery recovery period. In experiment 3, mice will be fully anesthesized until euthanasia during the instestinal loop surgery.