Frontiers in Neuroscience (Jan 2022)
Systematic Phenotyping and Characterization of the 3xTg-AD Mouse Model of Alzheimer’s Disease
- Dominic I. Javonillo,
- Kristine M. Tran,
- Kristine M. Tran,
- Jimmy Phan,
- Edna Hingco,
- Enikö A. Kramár,
- Celia da Cunha,
- Stefania Forner,
- Shimako Kawauchi,
- Giedre Milinkeviciute,
- Angela Gomez-Arboledas,
- Jonathan Neumann,
- Crystal E. Banh,
- Michelle Huynh,
- Dina P. Matheos,
- Narges Rezaie,
- Narges Rezaie,
- Joshua A. Alcantara,
- Ali Mortazavi,
- Ali Mortazavi,
- Marcelo A. Wood,
- Andrea J. Tenner,
- Andrea J. Tenner,
- Andrea J. Tenner,
- Andrea J. Tenner,
- Grant R. MacGregor,
- Grant R. MacGregor,
- Kim N. Green,
- Kim N. Green,
- Frank M. LaFerla,
- Frank M. LaFerla
Affiliations
- Dominic I. Javonillo
- Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United States
- Kristine M. Tran
- Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United States
- Kristine M. Tran
- Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, United States
- Jimmy Phan
- Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United States
- Edna Hingco
- Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United States
- Enikö A. Kramár
- Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, United States
- Celia da Cunha
- Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United States
- Stefania Forner
- Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United States
- Shimako Kawauchi
- Transgenic Mouse Facility, University Laboratory Animal Resources, Office of Research, University of California, Irvine, Irvine, CA, United States
- Giedre Milinkeviciute
- Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United States
- Angela Gomez-Arboledas
- Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, United States
- Jonathan Neumann
- Transgenic Mouse Facility, University Laboratory Animal Resources, Office of Research, University of California, Irvine, Irvine, CA, United States
- Crystal E. Banh
- Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United States
- Michelle Huynh
- Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United States
- Dina P. Matheos
- Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, United States
- Narges Rezaie
- Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, United States
- Narges Rezaie
- Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, United States
- Joshua A. Alcantara
- Transgenic Mouse Facility, University Laboratory Animal Resources, Office of Research, University of California, Irvine, Irvine, CA, United States
- Ali Mortazavi
- Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, United States
- Ali Mortazavi
- Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, United States
- Marcelo A. Wood
- Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, United States
- Andrea J. Tenner
- Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United States
- Andrea J. Tenner
- Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, United States
- Andrea J. Tenner
- Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, United States
- Andrea J. Tenner
- Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA, United States
- Grant R. MacGregor
- Transgenic Mouse Facility, University Laboratory Animal Resources, Office of Research, University of California, Irvine, Irvine, CA, United States
- Grant R. MacGregor
- Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, United States
- Kim N. Green
- Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United States
- Kim N. Green
- Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, United States
- Frank M. LaFerla
- Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United States
- Frank M. LaFerla
- Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, United States
- DOI
- https://doi.org/10.3389/fnins.2021.785276
- Journal volume & issue
-
Vol. 15
Abstract
Animal models of disease are valuable resources for investigating pathogenic mechanisms and potential therapeutic interventions. However, for complex disorders such as Alzheimer’s disease (AD), the generation and availability of innumerous distinct animal models present unique challenges to AD researchers and hinder the success of useful therapies. Here, we conducted an in-depth analysis of the 3xTg-AD mouse model of AD across its lifespan to better inform the field of the various pathologies that appear at specific ages, and comment on drift that has occurred in the development of pathology in this line since its development 20 years ago. This modern characterization of the 3xTg-AD model includes an assessment of impairments in long-term potentiation followed by quantification of amyloid beta (Aβ) plaque burden and neurofibrillary tau tangles, biochemical levels of Aβ and tau protein, and neuropathological markers such as gliosis and accumulation of dystrophic neurites. We also present a novel comparison of the 3xTg-AD model with the 5xFAD model using the same deep-phenotyping characterization pipeline and show plasma NfL is strongly driven by plaque burden. The results from these analyses are freely available via the AD Knowledge Portal (https://modeladexplorer.org/). Our work demonstrates the utility of a characterization pipeline that generates robust and standardized information relevant to investigating and comparing disease etiologies of current and future models of AD.
Keywords
- Alzheimer’s disease
- amyloid β-protein
- tau
- neurofibrillary tangles
- amyloid precursor protein
- animal model
