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

ABSTRACT: 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.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE12672 | GEO | 2009/08/25

SECONDARY ACCESSION(S): PRJNA112743

REPOSITORIES: GEO

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Project description:Bone mineral density and structure candidate gene analysis in alcohol-non-preferring (NP), alcohol-preferring (P), congenic NP (NP.P) and congenic P (P.NP) rats Genetic mapping in alcohol-preferring (P) and alcohol-non-preferring (NP) rats has identified a major quantitative trait locus (QTL) in the region between q22 – q34 on chromosome (Chr) 4 for alcohol preference. In a separate genome-wide linkage study, using inbred Fischer 344 (F344) and Lewis (LEW) rats, several QTL linked to bone density and structure were identified at the same location suggesting that bone mass and strength genes might co-segregate with genes that regulate the alcohol preference trait. The aim of this study is to identify the genes segregating for skeletal phenotypes and alcohol trait in congenic P/NP rats. We compared bone mineral content (BMC), areal/volumetric bone mineral density (aBMD/vBMD) and biomechanical strength at different skeletal sites from 6-month-old inbred and congenic P/NP rats. Transfer of the NP Chr 4 QTL into P background significantly increased body weight but decreased BMC, aBMD/vBMD in whole body, cranium, femur, and lumbar vertebrae. On the other hand, transfer of P Chr 4 QTL into NP background significantly decreased body weight but increased BMC and aBMD in the same skeletal sites. Microarray analysis was performed from the femurs of 4-week-old rats (n = 5 per strain) using Affymetrix Rat Genome 230 2.0 arrays. A total of 53 genes, including 41 candidate genes and 12 predicted genes, were differentially expressed among all strains of rats with a false discovery rate (FDR) less than 10%. Several candidate genes from microarray analysis were found to be were strongly correlated (r2>0.50) with different skeletal phenotypes. Gene expression of top 3 candidate genes from microarray profiling was validated by quantitative real-time PCR (qRT-PCR). Ingenuity pathway analysis revealed relationships among the candidate genes related to bone metabolism including pathways related to beta-estradiol, tumor necrosis factor and androgen receptor. Keywords: Comparison of gene expression profiles between NP, P, NP.P and P.NP rats

Project description:Bone mineral density and structure candidate gene analysis in alcohol-non-preferring (NP), alcohol-preferring (P), congenic NP (NP.P) and congenic P (P.NP) rats; Genetic mapping in alcohol-preferring (P) and alcohol-non-preferring (NP) rats has identified a major quantitative trait locus (QTL) in the region between q22 â?? q34 on chromosome (Chr) 4 for alcohol preference. In a separate genome-wide linkage study, using inbred Fischer 344 (F344) and Lewis (LEW) rats, several QTL linked to bone density and structure were identified at the same location suggesting that bone mass and strength genes might co-segregate with genes that regulate the alcohol preference trait. The aim of this study is to identify the genes segregating for skeletal phenotypes and alcohol trait in congenic P/NP rats. We compared bone mineral content (BMC), areal/volumetric bone mineral density (aBMD/vBMD) and biomechanical strength at different skeletal sites from 6-month-old inbred and congenic P/NP rats. Transfer of the NP Chr 4 QTL into P background significantly increased body weight but decreased BMC, aBMD/vBMD in whole body, cranium, femur, and lumbar vertebrae. On the other hand, transfer of P Chr 4 QTL into NP background significantly decreased body weight but increased BMC and aBMD in the same skeletal sites. Microarray analysis was performed from the femurs of 4-week-old rats (n = 5 per strain) using Affymetrix Rat Genome 230 2.0 arrays. A total of 53 genes, including 41 candidate genes and 12 predicted genes, were differentially expressed among all strains of rats with a false discovery rate (FDR) less than 10%. Several candidate genes from microarray analysis were found to be were strongly correlated (r2>0.50) with different skeletal phenotypes. Gene expression of top 3 candidate genes from microarray profiling was validated by quantitative real-time PCR (qRT-PCR). Ingenuity pathway analysis revealed relationships among the candidate genes related to bone metabolism including pathways related to beta-estradiol, tumor necrosis factor and androgen receptor. Experiment Overall Design: Comparison of differentially expressed genes between 4q22-4q34 on chromosome 4 in NP, P, NP.P and P.NP rats.

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

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