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Series GSE15892 Query DataSets for GSE15892
Status Public on Oct 21, 2010
Title Microarray data from control and pericyte-deficient mouse brain microvascular transcriptomes
Organism Mus musculus
Experiment type Expression profiling by array
Summary The blood-brain barrier (BBB) consists of specific physical barriers, enzymes and transporters, which together maintain the necessary extracellular environment of the central nervous system (CNS). The main physical barrier is found in the CNS endothelial cell, and depends on continuous complexes of tight junctions combined with reduced vesicular transport. Other possible constituents of the BBB include extracellular matrix, astrocytes and pericytes, but the relative contribution of these different components to the BBB remains largely unknown. Here we demonstrate a direct role of pericytes at the BBB in vivo. Using a set of adult viable pericyte-deficient mouse mutants we show that pericyte deficiency increases the permeability of the BBB to water and a range of low-molecular-mass and high-molecular-mass tracers. The increased permeability occurs by endothelial transcytosis, a process that is rapidly arrested by the drug imatinib. Furthermore, we show that pericytes function at the BBB in at least two ways: by regulating BBB-specific gene expression patterns in endothelial cells, and by inducing polarization of astrocyte end-feet surrounding CNS blood vessels. Our results indicate a novel and critical role for pericytes in the integration of endothelial and astrocyte functions at the neurovascular unit, and in the regulation of the BBB.
 
Overall design The brain microvascular fragments were isolated from mice with different genotypes, each represented by 3-4 biological replicates. Genotypes 1-2: Platelet derived growth factor-B (PDGF-B) retention-motif knockout (pdgfbret/ret) represent the pericyte-deficient situation, and the heterozygous mice (pdgfbret/+) are used as controls. Genotypes 3-4: Hypomorphic PDGF-B mutants that rescue pdgfb-/- null mice, in which a one copy of a conditionally silent human PDGF-B transgene targeted to the Rosa 26 locus (R26P) is turned on by endothelial-specific expression of Cre recombinase. In this data set these mice are named as Tie2Cre, R26P+/0, pdgfb-/- (representing the pericyte-deficient situation). Mice wt for pdgfb (pdgfb+/+) and carrying one silent copy of R26P (R26P+/0), are used as controls. Genotype 5: Adult Notch3+/+ wildtype (WT).
 
Contributor(s) Armulik A, Genové G, Mäe M, Nisancioglu MH, Wallgard E, Niaudet C, He L, Norlin J, Lindblom P, Strittmatter K, Johansson BR, Betsholtz C
Citation(s) 20944627
Submission date Apr 29, 2009
Last update date Feb 11, 2019
Contact name Elisabet Wallgard
E-mail(s) elisabet.wallgard@ki.se
Organization name Karolinska Institutet
Department Dept. of Medical Epidemiology and Biostatistics
Street address Nobels väg 12A, PO Box 281
City Stockholm
ZIP/Postal code SE-17177
Country Sweden
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (30)
GSM399040 pdgfbret/+ brain microvascular fragments, 8 months old, biological rep 1
GSM399041 pdgfbret/+ brain microvascular fragments, 8 months old, biological rep 2
GSM399042 pdgfbret/+ brain microvascular fragments, 8 months old, biological rep 3
Relations
BioProject PRJNA117061

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Supplementary file Size Download File type/resource
GSE15892_RAW.tar 117.6 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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