Seminar: Professor Takaomi Saido on mouse models in Alzheimer disease
Speaker: Professor Takaomi C. Saido, Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Japan
Animal models of human diseases that recapitulate their pathology in an accurate manner represent indispensable tools for understanding molecular mechanisms and for use in preclinical studies. For more than two decades, the Alzheimer’s disease (AD) research community has depended on transgenic (Tg) mouse models that overexpress mutant amyloid precursor protein (APP) or APP and presenilin (PS), mutations of which cause familial AD (FAD). These mice exhibit the pathological hallmarks of AD, but it is becoming clear that the overexpression of transgenes from artificial promotors may cause phenotypes that may not related to AD. The next-generation mouse models contain humanized sequences and clinical mutations in the endogenous mouse App gene, leading to Ab accumulation without overexpression of APP or PS, avoiding at least these problems. I will describe the different mouse models used to study AD including benefits and potential pitfalls. I will then propose the broad adaptation of these models and the use of similar strategies to generate additional models for other neurodegenerative disorders. I will also describe our current efforts to generate non-human primate (common marmoset) models using genome-editing technology.
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2. Fazzari et al., Nature (2017)