Generation and Characterization of the First Murine Model of Alzheimer's Disease with Mutated AβPP Inserted in a BALB/c Background (C.B6/J-APPswe)

第一个在 BALB/c 背景下植入突变 AβPP 的阿尔茨海默病小鼠模型 (C.B6/J-APPswe) 的生成和表征

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作者:Marta Balietti, Tiziana Casoli, Belinda Giorgetti, Roberto Colangeli, Cristina Nicoletti, Moreno Solazzi, Arianna Pugliese, Fiorenzo Conti

Background

Numerous mouse models of Alzheimer's disease (AD) are available, but all suffer from certain limitations, thus prompting further attempts. To date, no one model exists with amyloidopathy in a BALB/c strain.

Conclusion

C.B6/J-APPswe mice develop most of the distinctive features of AD and is a suitable model for the study of brain atrophy mechanisms and of the differences between males and females in the onset of cognitive/non-cognitive deficits.

Methods

We analyzed five groups at different ages (3, 6, 9, 12, and 16-18 months) of C.B6/J-APPswe and wild-type mice (50% males and 50% females) for the main hallmarks of AD by western blotting, amyloid-β (Aβ) ELISA, immunocytochemistry, electrophysiology, and behavioral tests.

Objective

To generate and characterize the C.B6/J-APPswe mouse, a model of AD with a mutated human gene for the amyloid-β protein precursor (AβPP) inserted in a BALB/c background.

Results

The C.B6/J-APPswe mouse displays early AβPP and Aβ production, late amyloid plaques formation, high level of Tau phosphorylation, synaptic deficits (reduced density and functional impairment due to a reduced post-synaptic responsiveness), neurodegeneration caused by apoptosis and necroptosis/necrosis, microgliosis, astrocytic abnormalities, and sex-related differences in explorative behavior, anxiety-like behavior, and spatial long-term and working memories. Social housing is feasible despite the intra-cage aggressiveness of male animals.

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