5 Modeling Cancer and Aging in the Telomerase-deficient Mouse

Abstract

The year 2007 will mark the centennial anniversary of mouse genetics. In these 100 years, repeated waves of technological innovation and genetic insight have positioned the mouse as a major experimental system for the study of complex human diseases and biological processes such as cancer, aging, and chronic degenerative disorders. The capacity to utilize the mouse to maximum experimental advantage stems from our capacity to precisely manipulate the mouse germ line, control and homogenize genetic variations, and assess genotype–phenotype associations in the context of the whole organism. Indeed, the mouse has contributed greatly to our understanding of the basis for virtually all major human diseases, shedding first light on central biological processes and often providing more surprises than fulfilled prophecies. At the same time, as with all model organisms, full utilization of the mouse necessitates an appreciation for cross-species similarities and differences in biology, genetics, and genomics and, where possible, how such differences can be exploited experimentally to dissect fundamental issues relating to key biological processes. In the study of telomeres and their roles in governing normal physiology and disease, it has been possible to take advantage of species-specific differences in mouse and human telomere dynamics to explore the relevance and specific contributions of telomeres and telomerase in biology and pathophysiology. As a result of efforts from many laboratories, the study of telomeres in the mouse has resulted in a steady stream of insights that are now being confirmed in human tissues with increasing regularity. It is reasonable to...