Abstract

Mouse models of human diseases are invaluable tools for studying pathogenic mechanisms and testing interventions and therapeutics. For disorders such as Alzheimer’s disease in which numerous models are being generated, a challenging first step is to identify the most appropriate model and age to effectively evaluate new therapeutic approaches. Here we conducted a detailed phenotypic characterization of the 5xFAD model on a congenic C57BL/6 J strain background, across its lifespan – including a seldomly analyzed 18-month old time point to provide temporally correlated phenotyping of this model and a template for characterization of new models of LOAD as they are generated. This comprehensive analysis included quantification of plaque burden, Aβ biochemical levels, and neuropathology, neurophysiological measurements and behavioral and cognitive assessments, and evaluation of microglia, astrocytes, and neurons. Analysis of transcriptional changes was conducted using bulk-tissue generated RNA-seq data from microdissected cortices and hippocampi as a function of aging, which can be explored at the MODEL-AD Explorer and AD Knowledge Portal. This deep-phenotyping pipeline identified novel aspects of age-related pathology in the 5xFAD model.

Measurement(s)

Protein Expression • gene expression • electrophysiology data • protein measurement • behavior

Technology Type(s)

immunofluorescence microscopy assay • RNA sequencing • electrophysiology assay • Electrochemiluminescence Immunoassay • animal activity monitoring system

Factor Type(s)

genotype • age • sex

Sample Characteristic - Organism

Mus musculus

Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.15176109

Details

Title
Systematic phenotyping and characterization of the 5xFAD mouse model of Alzheimer’s disease
Author
Forner Stefania 1   VIAFID ORCID Logo  ; Kawauchi Shimako 2 ; Balderrama-Gutierrez, Gabriela 3 ; Kramár, Enikö A 4 ; Matheos, Dina P 4 ; Phan, Jimmy 1 ; Javonillo, Dominic I 1 ; Tran, Kristine M 1 ; Hingco Edna 1 ; da Cunha Celia 1 ; Rezaie Narges 3   VIAFID ORCID Logo  ; Alcantara, Joshua A 2 ; Baglietto-Vargas, David 1 ; Jansen Camden 3 ; Neumann, Jonathan 2 ; Wood, Marcelo A 4 ; MacGregor, Grant R 5   VIAFID ORCID Logo  ; Mortazavi, Ali 3   VIAFID ORCID Logo  ; Tenner, Andrea J 6   VIAFID ORCID Logo  ; LaFerla, Frank M 7   VIAFID ORCID Logo  ; Green, Kim N 7 

1  University of California, Institute for Memory Impairments and Neurological Disorders (UCI MIND), Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243) 
2  University of California, Transgenic Mouse Facility, University Laboratory Animal Resources, Office of Research, Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243) 
3  University of California, Department of Developmental and Cell Biology, Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243); University of California, Center for Complex Biological Systems, Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243) 
4  University of California, Department of Neurobiology and Behavior, Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243) 
5  University of California, Transgenic Mouse Facility, University Laboratory Animal Resources, Office of Research, Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243); University of California, Department of Developmental and Cell Biology, Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243) 
6  University of California, Institute for Memory Impairments and Neurological Disorders (UCI MIND), Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243); University of California, Department of Neurobiology and Behavior, Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243); University of California, Department of Molecular Biology and Biochemistry, Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243); University of California, Department of Pathology and Laboratory Medicine, Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243) 
7  University of California, Institute for Memory Impairments and Neurological Disorders (UCI MIND), Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243); University of California, Department of Neurobiology and Behavior, Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20524463
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41597-021-01054-y
ProQuest document ID
2582277400
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.