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Transgenic APP expression during postnatal development causes persistent locomotor hyperactivity in the adult.
Shaefali P Rodgers1, Heather A Born, Pritam Das
1Department of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Molecular Neurodegeneration
|June 20, 2012
Summary
Early overexpression of Alzheimer's precursor protein (APP) in mice causes hyperactivity. Delaying APP transgene onset until adulthood significantly reduces this effect, highlighting developmental impacts on neurological function.
Area of Science:
- Neuroscience
- Genetics
- Animal Models
Background:
- Transgenic mice are crucial for studying neurological disorders.
- Continuous transgene expression can cause unintended phenotypes.
- This study investigates developmental effects of Alzheimer's precursor protein (APP) overexpression.
Purpose of the Study:
- To determine the impact of early versus late onset of amyloid precursor protein (APP) overexpression on mouse behavior.
- To understand how developmental exposure to transgenic APP influences neuronal circuits.
Main Methods:
- Utilized tet-off transgenic mice overexpressing the Alzheimer's-related amyloid precursor protein (APP).
- Manipulated the onset of transgene expression to occur either during early postnatal development or in adulthood.
- Assessed locomotor activity and anxiety-related behaviors (thigmotaxis) in open field tests.
Main Results:
- Early postnatal overexpression of APP led to severe locomotor hyperactivity.
- Delaying APP transgene onset until adulthood significantly attenuated this hyperactivity.
- The age of APP onset did not affect anxiety-related behaviors, suggesting specific circuit-related impacts.
Conclusions:
- Locomotor hyperactivity in some Alzheimer's disease models may stem from developmental APP overexpression.
- Foreign transgenes can interact with brain development, causing lasting functional changes.
- The tet-off APP model allows for delayed transgene expression to mitigate developmental confounds.

