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Positional identification of Adamts16 variants linked to inherited hypertension: knockdown of Adamts16 in NRK-52E cells

ABSTRACT: We 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. Keywords: Gene knockdown with siRNA

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE12724 | GEO | 2008/11/01

SECONDARY ACCESSION(S): PRJNA114129

REPOSITORIES: GEO

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Positional identification of Adamts16 variants linked to inherited hypertension: gene expression of congenic vs S rats

Project description:We 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. Keywords: Genetic modification, disease state analysis

2008-11-01 | GSE12725 | GEO

Transcription profiling of rat Adamts16 variants linked to inherited hypertension: gene expression of congenic vs S rats

Project description:We 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. Experiment Overall Design: Kidney RNA from 3 Dahl salt-sensitive rats was extracted for target preparation and hybridization onto Affymetrix GeneChips. We also isolated kidney RNA from 3 S.LEW(D1MCO4x1x3Bx1) congenic rats for target preparation and hybridization onto Affymetrix GeneChips.

2008-11-13 | E-GEOD-12725 | biostudies-arrayexpress

Transcription profiling of rat Adamts16 variants linked to inherited hypertension: knockdown of Adamts16 in NRK-52E cells

Project description:We 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. Experiment Overall Design: RNA from 3 independent cultures of NRK-52E cells treated with scrambled control siRNA was extracted for target preparation and hybridization onto Affymetrix GeneChips. We also isolated RNA from NRK-52E cells treated with two different siRNAs targeting Adamts16 (n=2 independent cultures for each siRNA) for target preparation and hybridization onto Affymetrix GeneChips.

2008-11-13 | E-GEOD-12724 | biostudies-arrayexpress

Identification of gene modulating vascular inflammation using chromosome 2 fragment substitutions and RNA sequencing [miRNA-Seq]

Project description:Chromosome 2 introgression from normotensive Brown Norway (BN) rats into hypertensive Dahl salt-sensitive (SS) background (consomic S2B) reduced blood pressure (BP) and vascular inflammation under normal salt diet (NSD). We hypothesized that BN chromosome 2 contains anti-inflammatory genes that could reduce BP elevation and vascular inflammation in rats fed NSD and high salt diet (HSD). We used chromosome 2 fragment substitutions to map chromosome 2 portion associated with vascular inflammation changes and next generation sequencing (NGS) to profile microRNAs in thoracic descending aorta of SS and congenic rats fed NSD or HSD.

2021-03-22 | GSE149515 | GEO

Transcription profiling of peritoneal fat of SHR/01a (spontaneously hypertensive rat), BN-Lx (Brown Norway congenic carrying polydactyly-luxate syndrome)and recombinant inbred (HXB/BXH) 6-week old rat strains

Project description:Gene expression profiling of peritoneal fat of SHR/01a (spontaneously hypertensive rat), BN-Lx (Brown Norway congenic carrying polydactyly-luxate syndrome)and recombinant inbred (HXB/BXH) 6-week old rat strains.

2010-11-18 | E-AFMX-7 | biostudies-arrayexpress

Identification of gene modulating vascular inflammation using chromosome 2 fragment substitutions and RNA sequencing [RNA-Seq]

Project description:Chromosome 2 introgression from normotensive Brown Norway (BN) rats into hypertensive Dahl salt-sensitive (SS) background (consomic S2B) reduced blood pressure (BP) and vascular inflammation under normal salt diet (NSD). We hypothesized that BN chromosome 2 contains anti-inflammatory genes that could reduce BP elevation and vascular inflammation in rats fed NSD and high salt diet (HSD). We used chromosome 2 fragment substitutions to map chromosome 2 portion associated with vascular inflammation changes and next generation sequencing (NGS) to profile messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) in thoracic descending aorta of SS and congenic rats fed NSD or HSD.

2021-03-22 | GSE149514 | GEO

Expression data from myocardial tissue from Spontaneously hypertensive rat (SHR) and its minimal congenic strain PD5

Project description:Spontaneously hypertensive rat (SHR; Rat Genome Database (RGD) ID: 631848) is probably the most commonly used rodent model for essential hypertension. Its minimal congenic subline PD5 ( SHR.PD-(D8Rat42-D8Arb23)/Cub; (RGD ID: 1641851)) which differs by a short segment of chromosome 8 (encompassing only 7 genes) displays lower levels of blood pressure and amelioration of cardiac fibrosis compared to SHR. We used microarray aproach to unravel gene expression differences between SHR and PD5 responsible for the different phenotypes in our rat strains.

2019-02-20 | GSE126709 | GEO

Renal gene expression analysis of rat malignant hypertensive end-organ damage

Project description:Severe forms of hypertension are characterized by high blood pressure combined with end-organ damage. Through the development and refinement of a transgenic rat model of malignant hypertension (MH) incorporating the mouse renin gene, we previously identified a quantitative trait locus (QTL) on chromosome 10, which affects malignant hypertension severity and morbidity. We next generated an inducible MH model where the timing, severity and duration of hypertension was placed under the control of the researcher, allowing development of and recovery from end-organ damage to be investigated. We have now generated novel consomic Lewis (L) and Fischer (F) rat strains with inducible hypertension, and additional strains, which are reciprocally congenic for the refined chromosome 10 QTL – FL (Fischer with a Lewis congenic region and LF (Lewis with a Fischer congenic region). We have captured a modifier of end-organ damage within the QTL and, using a range of bioinformatic, biochemical and molecular biological techniques, have identified Angiotensin converting enzyme (Ace) as the modifier of tissue microvascular injury. This SuperSeries is composed of the SubSeries listed below.

2009-08-25 | GSE12672 | GEO

Transcription profiling of BXH/HXB rat recombinant inbred strains derived from the spontaneously hypertensive rat (SHR/Ola) and the Brown Norway congenic strains carrying the polydactylyl-luxate mutation (BN-Lx)

Project description:BXH/HXB rat recombinant inbred (RI) strains are derived from the spontaneously hypertensive rat (SHR/Ola) and the Brown Norway congenic strains carrying the polydactylyl-luxate mutation (BN-Lx). Tissue from the apex of left ventricle of the heart was disected from 128 RI SHR/Ola and BN-Lx parental strains, RNA was extracted and labelled and hybridised to Affymetrix Rat Genome 230 2.0 Arrays.

2008-04-01 | E-MIMR-222 | biostudies-arrayexpress

Expression data from male and female Schlager hypertensive (BPH/2J) and normotensive (BPN/3J) kidneys

Project description:Analysis of kidneys from 12 week BPH/2J hypertensive and age matched normotensive BPN/3J controls - males and females. The results provide insights into the genes that are involved in hypertension in both males and females, as well as highlight mechanisms that underlye sex differences in hypertension. We show that female data can be used to refine candidate genes and pathways, as well as highlight potential mechanisms to explain the differences in prevalence and severity of disease between the sexes. Male and female kidneys from 12 week old hypertensive (BPH/2J) and normotensive (BPN/3J) mice were collected for RNA extraction and hybridization on Affymetrix microarrays. We used data obtained from male and female kidneys to identify common genes that are involved in the development of hypertension in males and females

2014-09-28 | E-GEOD-54015 | biostudies-arrayexpress

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