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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: 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.

ORGANISM(S): Callithrix jacchus

PROVIDER: GSE194005 | GEO | 2022/03/01

REPOSITORIES: GEO

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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: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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Profiling study of B cells from lymph nodes in miR-146a over-expression transgenic mice

Project description:B cells were isolated from wild type and miR-146a transgenic mice, and analyzed using microarray assay.WT1 and WT2 were samples repeats, so were TG1 and TG2 .

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2024-01-17 | PXD048549 | Pride

Evaluating the Efficacy of Small Molecules for Neural Differentiation of Common Marmoset ESCs and iPSCs

Project description:The common marmoset (marmoset; Callithrix jacchus) harbors various desired features as a non-human primate (NHP) model for neuroscience research. Recently, efforts have been made to induce neural cells in vitro from marmoset pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), which are characterized by their capacity to differentiate into all cell types from the three germ layers. Successful generation of marmoset neural cells is not only invaluable for understanding neural development and for modeling neurodegenerative and psychiatric disorders, but is also necessary for the phenotypic screening of genetically-modified marmosets. However, differences in the differentiation propensity among PSC lines hamper the applicability and the reproducibility of differentiation methods. To overcome this limitation, we evaluated the efficacy of small molecules for neural differentiation of marmoset ESCs (cjESCs) and iPSCs using multiple differentiation methods. By immunochemical and transcriptomic analyses, we confirmed that our methods using the small molecules are efficient for various differentiation protocols by either enhancing the yield of a mixture of neural cells including both neurons and glial cells, or a pure population of neurons. Collectively, our findings optimized in vitro neural differentiation methods for marmoset PSCs, which would ultimately help enhance the utility of the animal model in neuroscience.

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Follicular B (FoB) cells purified from miR-17-92 transgenic mice, stimulated with LPS/IL-4 for 13.5 or 25.5 hours

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The Transglutaminase-2 interactome in the APP23 mouse model of Alzheimer disease

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2022-02-22 | PXD030354 | Pride

Maternal weight affects placental DNA methylation of genes invovled in metabolic pathways in the common marmoset monkey (Callithrix jacchus)

Project description:Accumulating evidence suggests that dysregulation of placental DNA methylation (DNAm) is a mechanism linking maternal weight during pregnancy to metabolic programming outcomes. The common marmoset, Callithrix jaccus, is a platyrrhine primate species that has provided much insight into studies of the primate placenta, maternal condition, and metabolic programming, yet the relationships between maternal weight and placental DNAm are unknown. Here, we report genome-wide DNAm from term marmoset placentas using reduced representation bisulfite sequencing. We identified 74 genes whose DNAm pattern is associated with maternal weight during gestation. These genes are predominantly involved in energy metabolism and homeostasis, including regulation of glycolytic and lipid metabolic processes pathways.

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