Evidence from multiple linkage and genome-wide association studies suggest that human chromosome 2 (HSA2) contains alleles that influence blood pressure (BP). Homologous to a large segment of HSA2 is rat chromosome 9 (RNO9), to which a BP quantitative trait locus (QTL) was previously mapped. The objective of the current study was to further resolve this BP QTL. Eleven congenic strains with introgressed segments spanning <81.8kb to <1.33Mb were developed by introgressing genomic segments of RNO9 from the Dahl salt-resistant (R) rat onto the genome of the Dahl salt-sensitive (S) rat and tested for BP. The congenic strain with the shortest introgressed segment spanning <81.8kb significantly lowered BP of the hypertensive S rat by 25 mm Hg and significantly increased its mean survival by 45 days. In contrast, two other congenic strains had increased BP compared with the S. We focused on the <81.8kb congenic strain which represents the shortest genomic segment to which a BP QTL has been definitively mapped to date in any species. Sequencing of this entire region in both S and R rats detected 563 variants. The region did not contain any known or predicted rat protein coding genes. Further, a whole genome renal transcriptome analysis between S and the <81.8kb S.R congenic strain revealed alterations in several critical genes implicated in renal homeostasis. Taken together, our results provide the basis for future studies to examine the relationship between the candidate variants within the QTL region and the renal differentially expressed genes as potential causal mechanisms for BP regulation.
Defining a rat blood pressure quantitative trait locus to a &lt;81.8 kb congenic segment: comprehensive sequencing and renal transcriptome analysis.
Age, Specimen part
View SamplesTechnical replicates from BC3 and BCBL1 cell lines were treated with DMSO or 5 micromoles of lenalidomide for 24 hours.
Immunomodulatory drugs target IKZF1-IRF4-MYC axis in primary effusion lymphoma in a cereblon-dependent manner and display synergistic cytotoxicity with BRD4 inhibitors.
Cell line, Treatment
View SamplesWe report here that KSHV viral infection targets the NF-kB pathway which is crucial for cell survival. KSHV protein vFLIP K13 is known to directly interact with cellular protein NEMO of the NF-kB pathway. We used gene expression array to suggets that the interaction of K13 with NEMO is important to activate NF-kB pathway.
NEMO is essential for Kaposi's sarcoma-associated herpesvirus-encoded vFLIP K13-induced gene expression and protection against death receptor-induced cell death, and its N-terminal 251 residues are sufficient for this process.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Positional identification of variants of Adamts16 linked to inherited hypertension.
No sample metadata fields
View SamplesWe used Affymetrix GeneChips to expression profile rat kidney NRK-52E cells treated with control scrambled siRNA or siRNA specifically targeting Adamts16. The goal of this project was to identify the downstream genes regulated by Adamts16 (the function of Adamts16 has yet to be fully delineated). Gene expression differences resulting from these siRNA-mediated gene knockdown experiments will be compared to the gene expression profiling experiments comparing kidneys from Dahl salt-senstive hypertensive inbred strain versus less hypertensive S.LEW(D1MCO4x1x3Bx1) congenic strain. The S.LEW(D1MCO4x1x3Bx1) congenic animal is an S rat containing the LEWIS allele for Adamts16 instead of the S allele. Gene expression differences in the kidneys of S.LEW(D1MCO4x1x3Bx1) versus S are hypothesized to result from sequence differences between the S and LEWIS alleles for Adamts16. It is further hypothesized that allelic differences in Adamts16 in inbred rats is responsible for blood pressure variance. The downstream genes regulated by Adamts16 may provide insight pertaining to the mechanism of blood pressure differences.
Positional identification of variants of Adamts16 linked to inherited hypertension.
No sample metadata fields
View SamplesWe used Affymetrix GeneChips to expression profile kidneys from Dahl salt-senstive hypertensive inbred strain and less hypertensive S.LEW(D1MCO4x1x3Bx1) congenic strain to identify genes downstream of Adamts16 (the function of Adamts16 has yet to be fully delineated). The S.LEW(D1MCO4x1x3Bx1) congenic animal is an S rat containing the LEWIS allele for Adamts16 instead of the S allele. It is hypothesized that allelic differences in Adamts16 in inbred rats is responsible for blood pressure variance. We further hypothesize that gene expression differences in the kidneys of S.LEW(D1MCO4x1x3Bx1) versus S result from sequence differences between the S and LEWIS alleles of Adamts16. Lastly, the downstream genes differentially regulated by the Adamts16 alleles may provide insight pertaining to the mechanism of blood pressure differences. Gene expression differences resulting from these kidney comparisons will be compared to the gene expression profiling experiments comparing siRNA-mediated knockdown of Adamts16 in NRK-52E kidney cells versus scrambled siRNA control.
Positional identification of variants of Adamts16 linked to inherited hypertension.
No sample metadata fields
View SamplesIn this report, we have found that gata1 expressing erythroid cells contribute to a significant proportion of total body oxidative stress when animals were exposed to a strong pro-oxidant. RNA-seq of zebrafish under oxidative stress revealed the induction of tp53. Zebrafish carrying tp53 with mutation in its DNA binding domain were acutely sensitive to pro-oxidant exposure and displayed significant reactive oxygen species (ROS) and tp53-independent erythroid cell death resulting in an edematous phenotype. We found that a major contributing factor to ROS was increased basal mitochondrial respiratory rate without reserve. These data add to the concept that tp53, while classically a tumor suppressor and cell cycle regulator, has additional roles in controlling cellular oxidative stress. Overall design: We performed RNA-seq in two experiments. (1) Wild-type zebrafish embryos were exposed to 1-naphthol (vs no exposure) from 24 - 72 hpf (n = 5/group). (2) tp53 mutant zebrafish embryos were exposed to 1-naphthol (vs no exposure) from 24 - 72 hpf (n = 5/group).
TP53 Modulates Oxidative Stress in Gata1<sup>+</sup> Erythroid Cells.
No sample metadata fields
View SamplesMyosin IIa-deficient follicular B cells have a hyperactivated phenotype. To identify what pathways are regulated by myosin IIa, we performed RNA-seq of coding RNA on flow cytometry sorted follicular B cells from CD23Cre+Myh9fl/fl and CD23Cre+Myh9wt/fl mice. Overall design: B220+AA4.1-CD23+CD21lo follicular B cells were sorted from 3 CD23Cre+Myh9fl/fl and 3 CD23Cre+Myh9wt/fl mice and mRNA was isolated and sequenced.
Myosin IIa Promotes Antibody Responses by Regulating B Cell Activation, Acquisition of Antigen, and Proliferation.
Cell line, Subject
View SamplesIt is unclear how nanosecond electrical pulses affect gene expression.
Evaluation of the Genetic Response of U937 and Jurkat Cells to 10-Nanosecond Electrical Pulses (nsEP).
Specimen part, Cell line
View SamplesIt is unclear how nanosecond electrical pulses affect gene expression.
Evaluation of the Genetic Response of U937 and Jurkat Cells to 10-Nanosecond Electrical Pulses (nsEP).
Specimen part, Cell line
View Samples