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Home: Research: Compendia: Research Models
RESEARCH MODELS

Mice expressing pathogenic mutations of human genes have become a critical tool for biomedical research and drug discovery, and nowhere more so than in the Alzheimer field. The generation of research models that develop some of the pathologic hallmarks of Alzheimer's has given a sizable boost to drug discovery efforts, and has also raised many intriguing questions about the underlying disease process. Identical mutations result in surprisingly divergent phenotypes in different mouse strains. Why? No model perfectly mimics the human disease. Why?

To support investigators' efforts, we are compiling this list of research models that are relevant to understanding Alzheimer disease. Our goal is to provide a central publication forum for quickly reporting and updating data on all published models. We have designed tables to facilitate comparisons of different models and to provide information on the availability of each model.

We strive to keep these lists up to date and to improve our format and editorial annotation. In addition to screening the published literature, we depend on investigators to notify us of updates, corrections and to tell us what we can do to support their work. These compendia are collaborative endeavors involving many scientists, all of whom will be publicly credited for their contributions.

If you would like to be involved, please contact us.

 

EFFECTS OF GENETIC BACKGROUND
Genetic mouse background in to which the transgene is placed can have a significant effect on strain maintenance and on the results of behavioral tests. For example, sight impairment trait is found in FVB/N, CBA and C3H genetic backgrounds (which makes spatial learning and memory tests that depend on visual acuity such as the Morris water maze difficult). Among other backgrounds, a high incidence of tumors are found in the DBA and 129 mouse, a high level of aggression in the SJL inbred mice, and age-related deafness and age-dependent accumulation of lesions in C57 mice.

Concentrations of APP that produce amyloid plaques in outbred transgenic lines are lethal for inbred FVB/N or C57B6j mice. Most of the APP mice that I found are on FVB/N or C57B6j backgrounds. When APP transgenes were expressed in FVB/N mice, premature death was usually preceded by a variety of neurologic signs, including neophobia and thigmotaxic behavior. Mice with mixed C57B6j x SJL backgrounds that died prematurely showed no obvious behavioral abnormalities. Experiments have shown that male C57B6j x SJL sires overexpressing mutated human APP mated with FVB/N breeder exhibited neophobic or thigmotaxic behavior, while mated with the C57B6j breeder, there was no such abnormal behaviors observed.

REFERENCE
Carlson GA, Borchelt DR, Dake A, Turner S, Danielson V, Coffin JD, Eckman C, Meiners J, Nilsen SP, Younkin SG, Hsiao KK. Genetic modification of the phenotypes produced by amyloid precursor protein overexpression in transgenic mice. Hum Mol Genet 1997 Oct;6(11):1951-9. Abstract



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