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Temporal and spatially controlled APP transgene expression using Cre-dependent alleles.

Emily J Koller1, Melissa Comstock1, Jonathan C Bean1

  • 1Department of Neuroscience, Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA.

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|April 8, 2022
PubMed
Summary

Researchers developed new mouse models for Alzheimer's disease (AD) research. These models offer precise control over the timing and location of amyloid precursor protein (APP) expression, advancing AD pathology studies.

Keywords:
Alzheimer's diseaseAmyloid precursor proteinAmyloid βCre-dependentTransgenic mouse

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Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Alzheimer's disease (AD) research heavily relies on mouse models.
  • Existing models often lack precise control over the spatial and temporal expression of disease-driving proteins like amyloid precursor protein (APP).
  • Cre and CreER driver lines offer spatial and temporal gene control but are underutilized in neurodegeneration studies.

Purpose of the Study:

  • To present novel strategies for controlling APP expression in mouse models of Alzheimer's disease.
  • To leverage Cre and CreER driver lines for precise spatial and temporal control of AD pathology.
  • To facilitate more accurate modeling of amyloid pathology in Alzheimer's disease.

Main Methods:

  • Developed two distinct strategies to control APP expression using Cre/CreER systems.
  • Strategy 1: Combined a Cre driver with a tetracycline-transactivator (tTA)-dependent APP responder via a Cre-to-tTA converter line for CreER-based control.
  • Strategy 2: Created a new mouse line with APP expression controlled by Cre recombinase through a lox-stop-lox cassette.

Main Results:

  • Demonstrated successful spatial and temporal control over APP expression using the CreER system and the converter line.
  • Showcased a new mouse line enabling direct Cre-mediated control of APP expression.
  • Established that mating the new allele with a CreER driver allows precise control over APP expression and subsequent amyloid onset.

Conclusions:

  • The developed strategies enable precise spatial and temporal control of APP expression in mouse models.
  • These tools enhance the ability to study Alzheimer's disease amyloid pathology with greater experimental accuracy.
  • The new mouse models offer significant advantages for investigating the mechanisms and potential treatments for Alzheimer's disease.