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Multimodal analyses of a non-human primate model harboring mutant amyloid precursor protein transgenes driven by the human EF1α promoter [WGS]

ABSTRACT: Multimodal analyses of a non-human primate model harboring mutant amyloid precursor protein transgenes driven by the human EF1α promoter [WGS]

PROVIDER: PRJNA798728 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17666240.fastq.gz	Fastqsanger.gz
	SRR17666241.fastq.gz	Fastqsanger.gz

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Multimodal analyses of a non-human primate model harboring mutant amyloid precursor protein transgenes driven by the human EF1α promoter

Project description:Multimodal analyses of a non-human primate model harboring mutant amyloid precursor protein transgenes driven by the human EF1α promoter

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Multimodal analyses of a non-human primate model harboring mutant amyloid precursor protein transgenes driven by the human EF1α promoter [RNA-seq]

Project description:Multimodal analyses of a non-human primate model harboring mutant amyloid precursor protein transgenes driven by the human EF1α promoter [RNA-seq]

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Multimodal analyses of a non-human primate model harboring mutant amyloid precursor protein transgenes driven by the human EF1α promoter [WGS]

Project description: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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Multimodal analyses of a non-human primate model harboring mutant amyloid precursor protein transgenes driven by the human EF1α promoter [RNA-seq]

2022-03-01 | GSE192674 | GEO

Multimodal analyses of a non-human primate model harboring mutant amyloid precursor protein transgenes driven by the human EF1α promoter

Project description:This SuperSeries is composed of the SubSeries listed below.

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Transcriptomic analysis of the spinal cords of knock-in adult mice carrying the ATXN2/TDP-43 human transgenes

Project description:Intermediate-length repeat expansions in ATAXIN-2 (ATXN2) are a strong genetic risk factor for amyotrophic lateral sclerosis (ALS). At the molecular level, ATXN2 intermediate expansions enhance TDP-43 toxicity and pathology. However, whether this triggers ALS pathogenesis at the cellular and functional level remains unknown. To investigate gene expression changes and deregulated pathways caused by ataxin-2 intermediate repeat expansions in presence/absence of mutant TDP-43, we performed RNA sequencing of whole spinal cords from knock-in mice harboring ATXN2 and TDP-43 human transgenes as well as non-transgenic mice (NTg)

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Transcriptomic changes mediated by β-amyloid in human aortic endothelial cells (HAOEC)

Project description:We found that β-amyloid accumulation is modulated in HAOEC cells by overexpression or blocking of lncRNA BACE1-AS, which in turn regulates both BACE1 mRNA and protein expression. BACE1 is key-enzyme in the synthesis of β-amyloid from Amyloid Precursor Protein (APP). The transcriptomic changes mediated by 400nM β-amyloid was investigated in HAOEC cells.

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