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| Status |
Public on Mar 01, 2022 |
| Title |
Multimodal analyses of a non-human primate model harboring mutant amyloid precursor protein transgenes driven by the human EF1α promoter [WGS] |
| Organism |
Callithrix jacchus |
| Experiment type |
Other
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| Summary |
Alzheimer’s disease (AD) is the first leading cause of dementia which afflicts tens of millions of people worldwide. Despite many scientific progresses to dissect the molecular basis of AD from studies on various mouse models, it has been suffered from evolutionary species differences between mice and humans. Here, we report generation of a non-human primate, common marmoset (marmoset; Callithrix jacchus) model that ubiquitously expresses Amyloid-beta precursor protein (APP) transgenes with the Swedish (KM670/671NL) and Indiana (V717F) mutations. We generated two female transgenic marmosets (TG1 and TG2), whose transgene integration was thoroughly investigated by genomic PCR, whole genome sequencing (WGS) and Fluorescence in situ hybridization (FISH) analyses. Using the reprogramming technology, we confirmed the validity of the transgene expression in induced neurons in vitro. Moreover, we discovered structural changes in specific brain regions of transgenic marmosets by magnetic resonance imaging (MRI) analysis, including in the entorhinal cortex and hippocampus. In postmortem histological analysis, we detected increased Aβ plaque formation in the TG1 cerebrum at the age of 7 years, although evident neuronal loss or glial inflammation was not observed. Thus, this study summarizes our attempt to establish a non-human primate model of AD, which may be beneficial for drug development and further disease modeling in combination with other genetically engineered models.
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| Overall design |
Whole genome sequencing of fibroblasts derived from transgenic marmosets.
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| Contributor(s) |
Yoshimatsu S, Sanosaka T, Okano H |
| Citation missing |
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| Submission date |
Jan 19, 2022 |
| Last update date |
Mar 01, 2022 |
| Contact name |
Sho Yoshimatsu |
| E-mail(s) |
yoshima@a7.keio.jp
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| Organization name |
Keio University School of Medicine
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| Department |
Physiology
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| Lab |
Hideyuki Okano's Lab
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| Street address |
35 Shinanomachi
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| City |
Shinjuku |
| State/province |
Tokyo |
| ZIP/Postal code |
160-8582 |
| Country |
Japan |
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| Platforms (1) |
| GPL31253 |
DNBSEQ-G400 (Callithrix jacchus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE194006 |
Multimodal analyses of a non-human primate model harboring mutant amyloid precursor protein transgenes driven by the human EF1α promoter |
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| Relations |
| BioProject |
PRJNA798728 |
