Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Deletion of the Alzheimer’s disease risk associated Abi3 gene locus in mice results in obesity and systemic metabolic disruption

ABSTRACT: A rare coding variant was identified within the human ABI3 gene that is associated with increased risk of Alzheimer’s disease (AD). Following this discovery, we recently demonstrated that deletion of Abi3 gene locus notably exacerbates AD neuropathology in the 5xFAD transgenic mouse model of amyloidosis. In the course of a related investigation into the functional impact of Abi3 deletion in mice, we made an unexpected discovery regarding the impact of Abi3 deletion on the non-transgenic littermates of those 5xFAD mice. In those mice, we found that deletion of Abi3 gene locus resulted in an obese phenotype. Therefore, we investigated this serendipitous discovery. In this report, we demonstrate that mice lacking Abi3 have dramatically increased body weight and body fat. Further, we determined that these mice without Abi3 have reduced energy expenditure. Additionally, we found that deletion of the Abi3 gene locus altered gene expression, particularly within immune pathways, within the hypothalamus. Subsequent immunohistological analysis of the central nervous system (CNS) revealed that microglia number and area were decreased specifically within the mediobasal hypothalamus of mice without Abi3. Altogether, this investigation establishes the functional importance of the Abi3 gene locus, particularly within the CNS, in the regulation of systemic metabolism and maintenance of healthy weight.

ORGANISM(S): Mus musculus

PROVIDER: GSE212299 | GEO | 2022/12/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Deletion of Abi3 gene locus exacerbates neuropathological features of Alzheimer’s disease in a mouse model of Aβ amyloidosis

Project description:Recently, large-scale human genetics studies identified a rare coding variant in the ABI3 gene that is associated with an increased risk of late-onset Alzheimer’s disease (AD). However, pathways by which ABI3 contributes to the pathogenesis of AD are unknown. To address this critical question, we determined whether loss of ABI3 function affects pathological features of AD in the 5XFAD mouse model. We demonstrate that the deletion of Abi3 locus significantly increases amyloid-b (Ab) accumulation and decreases microglia clustering around the plaques. Furthermore, long-term potentiation is impaired in 5XFAD;Abi3 knock-out (“Abi3-/-”) mice. Moreover, we identified dramatic changes in the proportion of microglia subpopulations in Abi3-/- mice using a single-cell RNA sequencing approach. Mechanistic studies demonstrate that Abi3 knockdown in microglia impairs migration and phagocytosis. Taken together, our study provides the first in vivo functional evidence that loss of ABI3 function may increase the risk of developing AD by affecting Ab accumulation and neuroinflammation.

2021-11-10 | GSE175389 | GEO

Deletion of Abi3 gene locus exacerbates neuropathological features of Alzheimer’s disease in a mouse model of Aβ amyloidosis

Project description:Recently, large-scale human genetics studies identified a rare coding variant in the ABI3 gene that is associated with an increased risk of late-onset Alzheimer’s disease (AD). However, pathways by which ABI3 contributes to the pathogenesis of AD are unknown. To address this critical question, we determined whether loss of ABI3 function affects pathological features of AD, such as amyloid- (A) accumulation, inflammation, and synaptic dysfunction, in the 5XFAD mouse model. We demonstrate that the deletion of Abi3 locus significantly increases levels of soluble and insoluble A and amyloid plaques and decreases microglia clustering around the plaques. Furthermore, long-term potentiation is impaired in Abi3 knock-out (Abi3-/-) mice. Nanostring-based transcriptomic analyses indicate that genes involved in microglial phagocytosis and immune response pathways are dysregulated in Abi3-/-mice. Moreover, we identified dramatic changes in microglia subpopulations in Abi3-/- mice using a single-cell RNA sequencing approach. Taken together, our study provides the first in vivo functional evidence that loss of ABI3 function may increase the risk of developing AD by affecting A pathway and neuroinflammation.

2021-11-04 | GSE159866 | GEO

Limited effects of an eIF2αS51A allele on neurological impairments in the 5xFAD mouse model of Alzheimer’s disease

Project description:Transcriptome analysis of hippocampal RNA samples from wild-type, 5xFAD, 5xFAD;eIF2α+/S51A and eIF2α+/S51A mice Our transcriptome analyses showed clear transcriptional alterations in hippocampi of 5xFAD compared to wild type mice that were not corrected by the eIF2αS51A allele. Hemizygous 5xFAD mice, which were on a genetic background of B6/SJL, were crossed with eIF2α+/S51A mice (C57BL/6J background), to generate the offspring that was analyzed in the microarray. Hippocampal samples of 12 mice (4 groups: wild-type, 5xFAD, 5xFAD;eIF2α+/S51A and eIF2α+/S51A) were processed using Affymetrix Mouse Exon 1.0 ST platform. Array data was processed by Affymetrix Exon Array Computational Tool. No technical replicates were performed.

2013-09-10 | E-GEOD-50521 | biostudies-arrayexpress

RNA sequencing of microglia sorted form tamoxifen treated Sall1CreER/fl and control Sall1fl/fl mice

Project description:Microglia are the resident macrophages of the central nervous system (CNS). Gene profiling identified the transcriptional regulator Sall1 as a microglia signature gene. Given the high expression of Sall1 in microglia, we sought to identify its function in vivo. The Sall1CreER allele has been targeted into the Sall1 locus, therefore Sall1CreER/fl mice (heterozygous for both alleles) allow inducible ablation of Sall1 expression in microglia after tamoxifen treatment. We performed RNA-seq to examine gene expression profiles of microglia sorted from tamoxifen treated adult Sall1CreER/fl mice and Sall1fl/fl control littermates. Microglia were obtained with > 98% purity and the absence of Sall1 was confirmed in Sall1CreER/fl microglia. We could show that deletion of Sall1 in microglia in vivo resulted in the conversion of these cells from resting tissue macrophages into inflammatory phagocytes leading to altered neurogenesis and disturbed tissue homeostasis. Similar changes in gene expression profiles were found in Sall1-deficient microglia isolated from tamoxifen-treated Cx3cr1CreERSall1fl/fl mice. In these mice, deletion of Sall1 is targeted to CX3CR1+ myeloid cells including microglia and CNS-associated macrophages but not to any other CNS-resident cells. This indicated that Sall1 transcriptional regulation maintains microglia identity and physiological properties in the CNS.

2016-10-19 | E-MTAB-5077 | biostudies-arrayexpress

HOST MICROBIOTA REGULATE SELECTIVE MYELOID SUBSETS IN THE CENTRAL NERVOUS SYSTEM DURING HOMEOSTASIS AND DISEASE

Project description:The immune cells of the central nervous system (CNS) comprise parenchymal microglia and at the CNS border regions meningeal, perivascular and choroid plexus macrophages (summarized as CNS-associated macrophages, CAMs). Previous work has uncovered that microglial properties are strongly dependent on environmental signals from the commensal microbiota while its effect on CAMs remained unknown. By combining several microbiota manipulation approaches, genetic mouse models and single-cell RNA-sequencing, we comprehensively characterized CNS myeloid cell composition and function. Under steady-state, the transcriptional profile and numbers of choroid plexus macrophages were found to be tightly steered by complex microbiota. Divergently, perivascular and meningeal macrophages were affected to a lesser extent. An acute perturbation through viral infection evoked an attenuated immune response of all CAMs in germ-free mice. Additionally, we assessed CAMs in a more chronic pathological state in 5xFAD mice as a model for Alzheimer’s disease whereby exclusively perivascular macrophages displayed enhanced amyloid beta uptake in GF 5xFAD mice. Our results provide novel insights for understanding distinct microbiota-CNS macrophage interactions during health and perturbation that could potentially be targeted therapeutically.

2021-10-01 | GSE178956 | GEO

Restraint of IFN-γ expression through a distal silencer CNS–28 for tissue homeostasis

Project description:Interferon-gamma (IFN-gamma) is a key cytokine in response to viral or intracellular bacterial infection in mammals. While a number of enhancers are described to promote IFN-gamma responses, no silencers for the Ifng gene have been identified. By examining H3K4me1 histone modification in naïve CD4+ T cells within Ifng locus, we identified an unrecognized silencer (CNS–28) that is responsible for restraining Ifng expression. Mechanistic study further demonstrates that CNS–28 maintains Ifng silence by diminishing enhancer-promoter interactions within Ifng locus in a T-bet independent manner. Functionally, CNS–28 restrains Ifng transcription in Th1, Tc1, and NK cells during both innate and adaptive immune responses. Moreover, CNS–28 deficiency resulted in repressed type 2 responses due to elevated IFN-gamma expression, shifting Th1 and Th2 paradigm. Thus, CNS–28 activity ensures immune cell quiescence by cooperating with other regulatory cis elements within the Ifng gene locus to minimize autoimmunity.

2023-03-01 | GSE204946 | GEO

Deletion of the Alzheimer’s disease risk associated Abi3 gene locus in mice results in obesity and systemic metabolic disruption

Project description:Deletion of the Alzheimer’s disease risk associated Abi3 gene locus in mice results in obesity and systemic metabolic disruption

| PRJNA874925 | ENA

Transcriptomic response to adult hypothalamic deletion of Snord116

Project description:Snord116 deletion mouse models recapitulate aspects of the Prader-Willi Syndrome. In this study, we examine the gene expression changes in the mediobasal hypothalamus for mice which have an adult onset deletion of Snord116 in the mediobasal hypothalamus.

2017-12-31 | GSE106210 | GEO

scRNAseq and scATACseq of Cd45+ cells from brains of 5XFAD mice bearing distinct APOE alleles and across age

Project description:Here we analyze the gene expression and chromatin accessibility landscape of immune cells in the brains of 5XFAD mice, a common model of Alzheimer's disease, bearing knock-in of human APOE variants in the mouse APOE locus, and aged to 10, 20, 60, or 96 weeks of age.

2023-12-29 | GSE225503 | GEO

Expression data from WT and TREM2 deficient microglia in a mouse model of Alzheimer's disease

Project description:We examined the role of TREM2 on microglia responses to amyloid-beta deposition in a mouse model of Alzheimer's disease Microglia were FACS-purified from 8.5 month old WT, Trem2-/-, 5XFAD, and Trem2-/- 5XFAD mice

2015-03-13 | E-GEOD-65067 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data