Transgenic and Gene Targeted Models of Dementia

Animal models of disease in genetically manipulated mice are powerful tools in medical research, including the study of dementia. The time and expense required to make genetically altered mice is considerable, and the importance of this investment is amplified by the long time course of most studies of dementia. Investigators need to be able to make informed choices about the different strategies for transgenics and gene targeting in order to minimize unwanted variation, and to maximize fidelity to the disease. In recent years, large genomic fragments stably cloned in well-characterized libraries, the means to manipulate their sequence, and the ability to make transgenic mice from these clones in inbred strains have increased greatly the power of the transgenic mouse. In addition, new embryonic cell lines from the C57BL/6 inbred strain of mice have become widely adopted for gene targeting, allowing knockins, knockouts, and conditional alleles to be established on the standard C57BL/6 background much more expeditiously than in the past. These methods, the time required, and the probability of success are reviewed with respect to mouse models of dementia.