Question

1. Oncogenic mutations of the (hypothetical) PRO gene are present in many tumor types, and are associated with high rates of tumor cell proliferation. Several drug companies are therefore trying to develop agents that specifically inhibit the mutant PRO gene product without affecting the normal protein. One company has approached you to assist with in vivo studies to test the efficacy of this agent and its specificity for tumors with PRO mutations. What type of mouse model would you propose to use? Describe a mouse model that would allow you to test this hypothesis.

• For xenograft/allograft experiments, briefly describe the type of cell lines you might use and the experimental end points you would be looking at.
• For GEMs, briefly describe the type of mouse you would make (you don’t need to go into details about how the mouse is generated), and the experimental end points you would be looking at.

*Please type answer, written answers are often hard to read!

Answer 1

1) Using a mouse model which is mutated for PRO gene using CRISPR techniques can be used to find out the efficacy of drugs .

We have to check PRO gene mutation results in tumor development in the mouse or not and than if it developes drug treatment reduces the tumor size and tumor volume or not and immunohistochemistry/ RT PCR/ western blot of mutated PRO gene

2) mouse/other species cancer cell lines will be used in which PRO gene will be mutated and than injected into the mouse model and will be seen for tumor growth and than drug treatment to reduce tumor size and volume and also immunohistochemistry/RT PCR/ western blot to check weather the tumor has been reduced or not

3. Genetically engineered mouse ( GEM) mouse models are genetically modified to have same human gene mutation to study cancer therapies . End points include tumor reduction, histopathological techniques and western blot