Your colleague in the lab next door is studying the diseasecerebral cavernous malformations (CCM) and discovers that the humanhomologue of the worm exc12 gene (human gene is HEXC12) is mutatedin a small fraction of familial CCM patients. You decide tocollaborate to test if this gene has a CCM phenotype in mouse,cultured cells, and zebrafish models.
1. Explain how you would generate a mouse model.
2. Based on its sequence you hypothesize that HEXC12 encodes asa small GTPase exchange protein (GEF) that might regulate theactivity of RhoA or CDC42. Explain how you would test thishypothesis using cultured cells.
3. How would you determine if HEXC12 regulates the activity ofthe Rho kinase (ROCK) using cultured mammalian cells?
4. How would you determine if HEXC12 is required in theendothelium or surrounding smooth muscle for proper vasculardevelopment in the mouse?
5. To gain more insight into HEXC12 you decide to use zebrafishas a model system. Explain how you would determine if it has a CCMphenotype in fish.
