Engineered Mouse Models and Identifying

This undergraduate lecture course will introduce how transgenic and mutant mouse models are generated and their utility in defining the functional roles of genes in vivo.  Classically, the function of a gene is tested in vivo by either overexpressing or inactivating its expression, leading to a gain-of-function or loss-of-function phenotype from which is inferred a gene’s normal role in homeostasis.  Here we will explore the classic strategies for the generation of transgenic and knockout mice, comparing and contrasting their individual strengths and weaknesses, while exploring the phenotypes that have resulted from these changes in gene expression.  Using a subset of primary papers, students will be introduced to research analysis to become more versed in the layers of experimental design needed to identify a gene’s function in vivo.   The theoretical timing and the strategy needed to design such experiments with these transgenic and mutant mouse models, and the power of stem cell experiments will be discussed.    

In addition, to develop critical and additional analytical skills, students will become versed in basic tissue histology and immunohistochemistry, using processed paraffin-embedded mouse tissues from wild-type and engineered mutant mouse lines.  Students will learn how to recognize numerous, normal adult tissues with light microscopy and to identify proliferative zones vs. fully differentiated layers within each.  In addition, they will analyze the development of mid-to-late gestational embryos in serial sections, to underscore the coordinated transformation of tissues required for normal embryonic development.  Finally, serial sections from well-defined mutant mouse models will used to identify and characterize abnormal phenotypes resulting from the knock-out of genes encoding cell cycle regulators or tumor suppressors.  Live animal handling or experimentation is not a component of this course.