A new line of mice promises to circumvent many of the problems of existing models by recapitulating much of the pathology seen in presymptomatic Alzheimer’s, without overexpressing APP or interrupting other mouse genes.
Over the last two decades, researchers have generated dozens of different mouse models of Alzheimer’s disease. The most commonly used lines carry mutant forms of human Abeta precursor protein (APP), either alone or in combination with human presenilin, tau, or other genes.
Used for both basic research and drug discovery, these animals have provided a wealth of information. However, there have been niggling doubts from the beginning that some of their phenotypes may have little to do with the human disease, and negative clinical trials later reinforced critical debate about the validity of overexpression models.
For example, some models can only be maintained on specific genetic backgrounds, some die young or have surprising phenotypes when crossed with other mouse lines, and in others amyloidosis drifts later in successive generations, suggesting gene expression changes from parents to offspring.
Enter a new line of mice that promises to circumvent many of these problems. Researchers led by Takaomi Saido have engineered APP knock-ins. These animals recapitulate much of the pathology seen in presymptomatic AD, without overexpressing APP or interrupting other mouse genes. How do these knock-ins compare? Click on the link below: