Mouse Models in Biomedical Research

The five concluding chapters (Chapters 14-18) provide insight into the work that needs to be done, after the mouse model has been generated. Chapter 14 provides an overview of the pathology studies that should be completed with every new mouse strain generated. Often, transgenic mice are only examined for the presence of predicted phenotypes. It is important, however, to asses the complete mouse for abnormalities. Although one could not apply all possible phenotyping methods to every new mouse model, it is advisable to carry out pathology studies according to the protocols provided.

The remaining four chapters provide some entry points into the four fields of research addressed here, i.e., immunology (Chapter 15), atherosclerosis (Chapter 16), cancer (Chapter 17), and neurobiology (Chapter 18). Chapter 15 provides a protocol for bone marrow transplantation. At present, the use of bone marrow transplantation is not only restricted to immunologists, who are able to substitute part of the immune system of live mice. Other applications make use of the replacement of macrophages (atherosclerosis) or the introduction of somatic stem cells. Bone marrow transfer has also been used to develop the first gene therapy protocols using retroviral modified bone marrow. The most essential protocol for atherosclerosis studies is the measurement of the lesion area in the proximal aorta, which is provided here in detail. Chapters 17 and 18 review concepts regarding the use of transgenic models in cancer and neurobiology, illustrating many of the approaches that were outlined in the preceding chapters, e.g., the use of reporter genes and the Cre-LoxP system.

To conclude, I want to stress the importance of performing a broad analysis of the newly generated mouse models. For example, my own scientific background is in the field of atherosclerosis. At the time the first transgenic mouse was born in our laboratory, we had a specific desire to understand the role of a particular apolipoprotein mutant (APOE3Leiden) in lipoprotein metabolism. We initially underestimated the usefulness of this mouse model, because our attention was exclusively focused on the effects of APOE3Leiden on plasma lipid levels. It should be clear, however, that transgenic mouse models force researchers to stretch scientific horizons, because one studies the impact of the mutant allele on the entire animal, rather than on one particular aspect of metabolism. Some 10 years later, mouse models for lipoprotein metabolism are central to most studies on atherogenesis in the mouse, and these models also play a role in studying diabetes and obesity. To appreciate this potential of mouse models, it is advised to embark on these studies with a multidisciplinary team; the actual generation of the model takes less effort than the subsequent research that may originate from it.

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