Question 1:

1. You have been studying various oncogenes and tumor suppressorgenes in tumor cell lines in vitro, but would now like to addresscertain questions in mouse models in vivo. For each of thequestions below, briefly describe the type of mouse model you woulduse.
   • For xenograft/allograft experiments, briefly describe the typeof cell lines you might use and the experimental end points youwould 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 isgenerated), and the experimental end points you would be lookingat.

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

1. You are studying a (hypothetical) newly-described member of afamily of protein kinases (XYK6), which you suspect mayfunction as an oncogene, based upon the observation that specificpoint mutations (especially Thr489Asp) are sometimes seen in humanbreast tumors.You’ve queried the TCGA database and found that thismutation, when present, seems to be an “early” mutation, since itis seen as frequently in early-stage lesions as in later-stagetumors.You therefore hypothesize that it may be a driver mutationthat contributes to the process of breast cancerinitiation.Describe a mouse model that would allow you to test thishypothesis.
2. Oncogenic mutations of the (hypothetical) PRO gene arepresent in many tumor types, and are associated with high rates oftumor cell proliferation. Several drug companies are thereforetrying to develop agents that specifically inhibit the mutantPRO gene product without affecting the normal protein. Onecompany has approached you to assist with in vivo studies to testthe efficacy of this agent and its specificity for tumorswith PRO mutations. What type of mouse model would youpropose to use?