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Author Notes:

Correspondence: agcay@missouri.edu

CA was responsible for genotypic and phenotypic characterization of transgenic rats, statistical analysis of data, colony management, and writing the paper.

JJL generated lentiviral vectors and performed ELISA.

DK and TRS have conducted rat behavioral assessment and analysis.

YA and AWC generated transgenic rats.

YA designed the research, and contributed to the analysis of the data.

The authors would also like to thank Dr. Marcia Hart for helping assess brain histopathology.

The authors declare that they have no competing interests.

Subjects:

Research Funding:

This study was funded by a grant from Alzheimer Research Consortium and the University of Missouri startup funds.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • ALZHEIMERS-DISEASE
  • A-BETA
  • DEPOSITION
  • PATHOLOGY
  • OLIGOMERS
  • NEURONS
  • MODEL

Presenilin 1 transgene addition to amyloid precursor protein overexpressing transgenic rats increases amyloid beta 42 levels and results in loss of memory retention

Journal Title:

BMC Neuroscience

Volume:

Volume 17, Number 1

Publisher:

, Pages 46-46

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: We previously reported the production of transgenic rats (APP21 line) that over-express human amyloid precursor protein (APP) containing Swedish and Indiana mutations. In order to generate a better model for Alzheimer's disease (AD), the APP21 rat line was used to generate double transgenic line that over-expressed Presenilin 1 (PS1) with L166P mutation in addition to APP transgene (APP + PS1 line). Results: Thirty-two double transgenic founders were generated and the ultimate transgenic founder was selected based on PS1 transgene copy number and level of amyloid-beta (Aβ)42 peptide. The APP + PS1 double transgenic rats had 38 times more PS1 in brains compared to APP rats. Behavioral assessment using Barnes maze showed that APP + PS1 rats exhibited a larger learning and memory deficit than APP21 rats. Double transgenic rats also produced more Aβ42. Histological examination of the brains showed that the APP21 rat line displayed neurofibrillary tangles and in contrast, the APP + PS1 line showed chromatolysis in hippocampal neurons and neuronal loss in CA3 region of hippocampus. Conclusions: Due to the separate segregation of APP and PS1 transgenes in APP + PS1 double transgenic rats, this transgenic line may be a valuable model for studying the effects of various levels of APP and PS1 transgenes on various aspects of brain pathologies associated with the AD phenotype.

Copyright information:

© 2016 The Author(s). The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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