Investigation of the role of MAIT cells in cholestatic liver diseases
1. Purpose
Primary sclerosing cholangitis (PSC) is a chronic inflammatory biliary disease affecting both the intra- and extrahepatic biliary ducts in young individuals (30-40 years old). At present there is no medical treatment for PSC, due to the unclear pathogenesis. Our previous investigations have found MAIT cell antigens in bile from patients with PSC, and that bile duct injection of antigens (5-OP-RU) could induce cholangitis in a mouse model. Now we would like to survey the functional signature of liver MAIT cells in cholestatic liver disease mice models and also take the microbiome into account.
2. Distress
We expect the animals to experience a transient mild pain after surgery. The feeding model will not involve any painful procedures, but will result in a gradually and marked weight loss.
3. Expected benefit
Characterisation the function of liver MAIT cells in cholestatic liver diseases mice model, will contribute to the understanding of the pathophysiology of PSC, and ultimately lead to novel treatment options.
4. Number of animals, and species
Mus musculus, 692 animals in total.
5. 3R
The replacement option is not applicable since our hypothesis needs to be tested in a complete animal. Experiments without animals have already been performed.
The n-value is 9 in each group, the lowest possible number to ensure trustworthy repeatability.
The surgery is based upon the internal experience and experience from a large numbers of research groups, as this method is highly well established. Pain relief is included.
Primary sclerosing cholangitis (PSC) is a chronic inflammatory biliary disease affecting both the intra- and extrahepatic biliary ducts in young individuals (30-40 years old). At present there is no medical treatment for PSC, due to the unclear pathogenesis. Our previous investigations have found MAIT cell antigens in bile from patients with PSC, and that bile duct injection of antigens (5-OP-RU) could induce cholangitis in a mouse model. Now we would like to survey the functional signature of liver MAIT cells in cholestatic liver disease mice models and also take the microbiome into account.
2. Distress
We expect the animals to experience a transient mild pain after surgery. The feeding model will not involve any painful procedures, but will result in a gradually and marked weight loss.
3. Expected benefit
Characterisation the function of liver MAIT cells in cholestatic liver diseases mice model, will contribute to the understanding of the pathophysiology of PSC, and ultimately lead to novel treatment options.
4. Number of animals, and species
Mus musculus, 692 animals in total.
5. 3R
The replacement option is not applicable since our hypothesis needs to be tested in a complete animal. Experiments without animals have already been performed.
The n-value is 9 in each group, the lowest possible number to ensure trustworthy repeatability.
The surgery is based upon the internal experience and experience from a large numbers of research groups, as this method is highly well established. Pain relief is included.