Systematic phenotyping and characterization of the 5xFAD mouse model of Alzheimer's disease

被引：207

作者：

Forner, Stefania ^{[1
]}

Kawauchi, Shimako ^{[2
]}

Balderrama-Gutierrez, Gabriela ^{[3
,4
]}

Kramar, Eniko A. ^{[5
]}

Matheos, Dina P. ^{[5
]}

Phan, Jimmy ^{[1
]}

Javonillo, Dominic, I ^{[1
]}

Tran, Kristine M. ^{[1
]}

Hingco, Edna ^{[1
]}

da Cunha, Celia ^{[1
]}

Rezaie, Narges ^{[3
,4
]}

Alcantara, Joshua A. ^{[2
]}

Baglietto-Vargas, David ^{[1
]}

Jansen, Camden ^{[3
,4
]}

Neumann, Jonathan ^{[2
]}

Wood, Marcelo A. ^{[5
]}

MacGregor, Grant R. ^{[2
,3
]}

Mortazavi, Ali ^{[3
,4
]}

Tenner, Andrea J. ^{[1
,5
,6
,7
]}

LaFerla, Frank M. ^{[1
,5
]}

Green, Kim N. ^{[1
,5
]}

机构：

[1] Univ Calif Irvine, Inst Memory Impairments & Neurol Disorders UCI MI, Irvine, CA 92697 USA

[2] Univ Calif Irvine, Univ Lab Anim Resources, Off Res, Transgen Mouse Facil, Irvine, CA 92697 USA

[3] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA

[4] Univ Calif Irvine, Ctr Complex Biol Syst, Irvine, CA 92697 USA

[5] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA

[6] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA

[7] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92697 USA

来源：

SCIENTIFIC DATA | 2021年 / 8卷 / 01期

关键词：

NEURONAL LOSS; MICROGLIA; MICE; DEGENERATION; EXPRESSION; BEHAVIOR; MEMORY; BRAIN;

D O I：

10.1038/s41597-021-01054-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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, A beta 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.

引用

页数：16

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