Characterization of the blood-brain barrier in genetically diverse laboratory mouse strains
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA727020 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14410037.fastq.gz | Fastqsanger.gz | |||
| SRR14410038.fastq.gz | Fastqsanger.gz | |||
| SRR14410039.fastq.gz | Fastqsanger.gz | |||
| SRR14410040.fastq.gz | Fastqsanger.gz | |||
| SRR14410041.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 43 |
Similar Datasets
Project description:Genetic variation in the population has an influence on the manifestation of monogenic as well as multifactorial disorders, with the underlying genetic contribution dependent on several interacting variants. Common laboratory mouse strains used for modelling human disease lack the genetic variability of the human population. Therefore, outcomes of rodent studies show limited correlation with human disease. The functionality of brain vasculature is an important modifier of brain diseases. Importantly, the restrictive interface between blood and brain – the blood-brain barrier (BBB) serves as a major obstacle for CNS drug delivery. Using genetically diverse mouse strains, we aimed to investigate the phenotypic and transcriptomic variation of the intact BBB in different inbred mouse strains.We investigated the heterogeneity of brain vasculature in recently wild-derived mouse strains (CAST/EiJ, WSB/EiJ, PWK/PhJ) and long-inbred mouse strains (129S1/SvImJ, A/J, C57BL/6J, DBA/2J, NOD/ShiLtJ) using different phenotypic arms. We used immunohistochemistry and confocal laser microscopy followed by quantitative image analysis to determine vascular density and pericyte coverage in two brain regions – cortex and hippocampus. Using a low molecular weight fluorescence tracer, sodium fluorescein and spectrophotometry analysis, we assessed BBB permeability in young and aged mice of selected strains. For further phenotypic characterization of endothelial cells in inbred mouse strains, we performed bulk RNA sequencing of sorted endothelial cells isolated from cortex and hippocampus. We did not detect differences in cortical and hippocampal vessel density and pericyte coverage among all the investigated strains. The staining patterns of endothelial arteriovenous zonation markers were similar in different strains. BBB permeability to a small fluorescent tracer, sodium fluorescein, was also similar in different strains. Transcriptomic analysis of endothelial cells revealed that sex of the animal was a major determinant of gene expression differences. In addition, the expression level of several genes implicated in endothelial function and BBB biology differed between wild-derived and long-inbred mouse strains. Our analysis shows that although there were no major differences in parenchymal vascular morphology and BBB permeability between investigated mouse strains or sexes, transcriptomic differences of brain endothelial cells point to variation in gene expression of the intact BBB. These baseline variances might be confounding factors in pathological conditions that may lead to a differential functional outcome dependent on the sex or genetic polymorphism.
2021-08-03 | GSE173793 | GEO
Project description:BackgroundGenetic variation in a population has an influence on the manifestation of monogenic as well as multifactorial disorders, with the underlying genetic contribution dependent on several interacting variants. Common laboratory mouse strains used for modelling human disease lack the genetic variability of the human population. Therefore, outcomes of rodent studies show limited relevance to human disease. The functionality of brain vasculature is an important modifier of brain diseases. Importantly, the restrictive interface between blood and brain-the blood-brain barrier (BBB) serves as a major obstacle for the drug delivery into the central nervous system (CNS). Using genetically diverse mouse strains, we aimed to investigate the phenotypic and transcriptomic variation of the healthy BBB in different inbred mouse strains.MethodsWe investigated the heterogeneity of brain vasculature in recently wild-derived mouse strains (CAST/EiJ, WSB/EiJ, PWK/PhJ) and long-inbred mouse strains (129S1/SvImJ, A/J, C57BL/6J, DBA/2J, NOD/ShiLtJ) using different phenotypic arms. We used immunohistochemistry and confocal laser microscopy followed by quantitative image analysis to determine vascular density and pericyte coverage in two brain regions-cortex and hippocampus. Using a low molecular weight fluorescence tracer, sodium fluorescein and spectrophotometry analysis, we assessed BBB permeability in young and aged mice of selected strains. For further phenotypic characterization of endothelial cells in inbred mouse strains, we performed bulk RNA sequencing of sorted endothelial cells isolated from cortex and hippocampus.ResultsCortical vessel density and pericyte coverage did not differ among the investigated strains, except in the cortex, where PWK/PhJ showed lower vessel density compared to NOD/ShiLtJ, and a higher pericyte coverage than DBA/2J. The vascular density in the hippocampus differed among analyzed strains but not the pericyte coverage. The staining patterns of endothelial arteriovenous zonation markers were similar in different strains. BBB permeability to a small fluorescent tracer, sodium fluorescein, was also similar in different strains, except in the hippocampus where the CAST/EiJ showed higher permeability than NOD/ShiLtJ. Transcriptomic analysis of endothelial cells revealed that sex of the animal was a major determinant of gene expression differences. In addition, the expression level of several genes implicated in endothelial function and BBB biology differed between wild-derived and long-inbred mouse strains. In aged mice of three investigated strains (DBA/2J, A/J, C57BL/6J) vascular density and pericyte coverage did not change-expect for DBA/2J, whereas vascular permeability to sodium fluorescein increased in all three strains.ConclusionsOur analysis shows that although there were no major differences in parenchymal vascular morphology and paracellular BBB permeability for small molecular weight tracer between investigated mouse strains or sexes, transcriptomic differences of brain endothelial cells point to variation in gene expression of the intact BBB. These baseline variances might be confounding factors in pathological conditions that may lead to a differential functional outcome dependent on the sex or genetic polymorphism.
| S-EPMC8317333 | biostudies-literature
Project description:We measured genome-wide gene expression of embryonic stem cells derived from eight genetically diverse inbred mouse strains. We derived and cultured cells in LIF+2i media with feeders, and removed feeders prior to RNA collection. All lines were passage 6-8 when RNA was collected. We collected RNA from three biological replicate cell lines derived from each of the eight inbred mouse strains. For three strains (C57BL/6J, NOD, and PWD/PhJ), we obtained technical replicate RNA-Seq runs of each of the three biological replicate cell lines.
2020-08-13 | E-MTAB-7730 | biostudies-arrayexpress
Project description:RNA-Seq of mouse embryonic stem cells derived from genetically diverse inbred mouse strains
| PRJEB31648 | ENA
Project description:Punic people were genetically diverse with almost no Levantine ancestors
| PRJEB86313 | ENA
Project description:Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice
| PRJNA689305 | ENA
Project description:We report the use of RNA-Seq technique to characterize differences in the global transcritome between multiple genetically similar but phenotypically diverse poultry-associated field strains of S. Enteritidis grown in laboratory media at avian body temperature (42°C).
2013-12-13 | GSE46391 | GEO
Project description:This dataset compares the transcriptome of five laboratory yeast strains (S. cerevisiae) cultured under standardized laboratory consitions (early exponential growth, cultured in synthetic complete glucose media at 30ºC).
2025-02-13 | GSE289029 | GEO
Project description:The yeast Saccharomyces cerevisiae is a powerful model system that is often used to expand our understanding of cellular processes and biological functions. Although many genetically well-characterized laboratory strains of S. cerevisiae are available, they may have different genetic backgrounds which can confound data interpretation. Here, we profile and compare the proteomes of two common laboratory yeast background strains, W303 and BY4742, in both exponential and stationary growth phases using isobaric tag-based mass spectrometry. We quantified over 4,400 proteins, hundreds of which showed differences in abundance between strains and/or growth phases. Moreover, we used proteome-wide abundance to profile the mating type of the strains used in the experiment, the auxotrophic markers and associated metabolic pathways, as well as to investigate differences in particular classes of proteins, such as the pleiotropic drug resistance (PDR) proteins. This study is a valuable resource that offers insight into mechanistic differences between two common yeast background strains and can be used as a guide to select a background that is best suited for addressing a particular biological question.
2023-12-28 | PXD044388 | Pride
Project description:Strand-specific RNA-Seq from genetically diverse crosses of Drosophila melanogaster during embryogenesis
| PRJEB37085 | ENA