Question

Question 1:

1. You have been studying various oncogenes and tumor suppressor genes in tumor cell lines in vitro, but would now like to address certain questions in mouse models in vivo. For each of the questions below, briefly describe the type of mouse model you would use.
   • 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.

Note: there is no single right answer. However, try to select the model that would be most straight-forward way to initially address your question.

3. You are studying a (hypothetical) newly-described member of a family of protein kinases (XYK6), which you suspect may function as an oncogene, based upon the observation that specific point mutations (especially Thr489Asp) are sometimes seen in human breast tumors.You’ve queried the TCGA database and found that this mutation, when present, seems to be an “early” mutation, since it is seen as frequently in early-stage lesions as in later-stage tumors.You therefore hypothesize that it may be a driver mutation that contributes to the process of breast cancer initiation.Describe a mouse model that would allow you to test this hypothesis.
4. 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?

Answer 1

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