New transgenic mouse likely to advance Alzheimer's disease research

A new strain of mice develops, with age, damaging tangles of a normal protein called tau in neurons of the spinal cord, brain stem, and brain. Similar aggregations of the filamentous protein are a key feature in a number of devastating age-related neurological disorders, including Alzheimer's disease. In Alzheimer's disease, for example, the tau tangles and plaques of another protein called beta amyloid in certain neurons of the brain are regarded as the two signature signs of the disease.

The new mouse, which incorporates and overexpresses a human gene coding for the tau protein, is expected to enable scientists to make major strides in understanding the role of tau tangles in this important group of neurodegenerative diseases, referred to collectively as tauopathies. A report describing the mouse, developed by researchers at the University of Pennsylvania Medical Center, appears in the November 24 issue of Neuron.

"The mouse we have developed is the first true animal model for a family of diseases known as tauopathies, the most well-known of which is Alzheimer's disease," says Virginia M.-Y. Lee, PhD, senior author on the study, codirector of the Center for Neurodegenerative Disease Research, and the John H. Ware 3d Professor of Alzheimer's Research in the department of pathology and laboratory medicine. "This mouse isn't, in and of itself, a complete model for Alzheimer's disease, but it should help us better to understand the crucial role that tau tangles play in the progression of that disease, as well as a number of other debilitating neurodegenerative diseases."

Efforts are now under way at Penn to cross the tau mouse with an existing strain of mice that develops beta amyloid plaques to produce a mouse that would even more closely mimic Alzheimer's disease. Lee says her team also hopes to be able to "knock out," or delete, the mouse version of the tau gene from the mouse DNA, leaving only the human gene, in order to fully "humanize" the strai

Contact: Franklin Hoke
University of Pennsylvania School of Medicine

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