Mouse Models in PDAC Research

The Olive Laboratory conducts research using mouse models. The laboratory uses different types of mice to perform different experiments to answer different questions. The reason we use mouse models is because humans share nearly the same genome. Of the approximately 4,000 genes that have been studied, fewer than 10 are found in one species but not in the other. Mice have also been studied extensively and have shown to be an excellent experimental model. Therefore, using mice has been integral in our research. What makes mice a great experimental model is because we can breed them in a way that is beneficial to our research, and this can include: inserting or deleting certain genes. We are also able to use some mice that lack an immune system, which allows human tumors to be grown and studied inside the mouse . Having these options allows us to study and understand pancreatic cancer and also see how they respond to new drugs that are being developed. 

The mouse model our lab primarily uses is the KPC model. KPC stands for: Kras, p53, and Cre. Kras and p53 are two genes that are often mutated in human pancreatic tumors. Cre is a special tool gene that is used to control where Kras and p53 are turned on. In the KPC model, it is used to turn them on in the mouse pancreas; these mice then go on to spontaneously develop pancreatic cancer, beginning initially as PanIN precursor lesions, and slowly progressing to metastatic disease. The KPC mouse model has been genetically modified, or in other words engineered in a laboratory to spontaneously grow pancreatic tumors. This is important because the development of cancer in humans is also a spontaneous event. In most cases, humans don't "catch" cancer. Not only is this spontaneity important for studying pancreatic cancer but the KPC mouse model shares other similarities to patients diagnosed with pancreatic ductal adenocarcinoma. One similarity is the mice develop similar symptoms to humans such as: weight loss, muscle loss, yellowing of the skin, and fluid build up in the abdomen. A second similarity is the tumors metastasize or spread to other organs such as the liver and the lungs. A third similarity is their appearance when studying the tumors under a microscope. The tumor cells in KPC mice look very similar to human pancreatic tumor cells and even the proteins and genes that are altered or turned on in the tumor are comparable to human PDA. Finally, pancreatic tumors in KPC mice tend to be very resistant to chemotherapy, just like human pancreatic tumors.  

Other mouse models we use are immunodeficient mice (mice without an immune system). These mice are typically used to grow samples of pancreatic tumors from specific patients, yielding a model called a patient derived xenograft (PDX). We use PDX models when patients consent to letting us use their biopsy samples to study in mice. Using mice without immune systems are important because otherwise the mouse immune system would reject the tumor. These mice are typically used to test different drugs that might be useful in the clinic. 

For a more scientific description of the KPC mouse model please see below.