Genetically engineered mouse models of neurodegenerative diseases


Recent research has significantly advanced our understanding of the molecular mechanisms of neurodegenerative diseases, including Alzheimer's disease (AD) and motor neuron disease. Here we emphasize the use of genetically engineered mouse models that are instrumental for understanding why AD is a neuronal disease, and for validating attractive therapeutic targets. In motor neuron diseases, Cu/Zn superoxide dismutase and survival motor neuron mouse models are useful in testing disease mechanisms and therapeutic strategies for amyotrophic lateral sclerosis (ALS) and spinal motor atrophy, respectively, but the mechanisms that account for selective motor neuron loss remain uncertain. We anticipate that, in the future, therapies based on understanding disease mechanisms will be identified and tested in mouse model systems.

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Figure 1: Pathological features of Alzheimer's disease.

Bob Crimi

Figure 2: Amyloid precursor protein (APP) and secretase cleavages.

Amy Center


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The authors thank colleagues from JHMI, particularly S. Sisodia, M. Lee, G. Thinakaren, E. Koo, J. Subramaniam, L. Martin, V. Koliatsos, A. Bergin, L. Brujin, C. Pardo, B. Rabin, T. Crawford, M. Becher, P. Hoffman, J. Griffin, J. Rothstein, J. Troncoso, T. Li, V. Culotta and D. Cleveland as well as those at other institutions (J. Gitlin) for contributions to the original work cited in this review and for discussions. Supported by grants from the U. S. Public Health Service (AG05146, AG07914, AG10480, AG10491, AG14248, NS07435, NS20471, NS37145, NS10580, NS37771, NS40014, NS38377, NS38065) as well as the Metropolitan Life Foundation, Adler Foundation, and Bristol-Myers Squibb Foundation.

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Correspondence to Philip C. Wong.

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Wong, P., Cai, H., Borchelt, D. et al. Genetically engineered mouse models of neurodegenerative diseases. Nat Neurosci 5, 633–639 (2002).

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