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Title: Downregulation of Plzf gene ameliorates metabolic and cardiac traits in the spontaneously hypertensive rat      
dateReleased:
07-03-2016
description:
The spontaneously hypertensive rat (SHR) is the most widely used model of essential hypertension and is predisposed to left ventricular hypertrophy, myocardial fibrosis, and metabolic disturbances. Recently, a quantitative trait locus (QTL) influencing blood pressure, left ventricular mass and heart interstitial fibrosis was genetically isolated within 788 kb on chromosome 8 segment of SHR-PD5 congenic strain that contains only 7 genes, including mutant Plzf (promyelocytic leukemia zinc finger) gene. To identify Plzf as a quantitative trait gene, we targeted Plzf in the SHR using the TALEN technique and obtained SHR line harboring mutant Plzf gene with a premature stop codon at position of amino acid 58. The Plzf mutant allele is semi-lethal since approximately 95% of newborn homozygous animals die perinatally due to multiple developmental abnormalities. Heterozygous rats were grossly normal and were used for metabolic and hemodynamic analyses. SHR-Plzf+/- heterozygotes versus SHR wild type controls exhibited reduced body weight and relative weight of epididymal fat, lower serum and liver triglycerides and cholesterol and better glucose tolerance. In addition, SHR-Plzf+/- rats exhibited significantly increased sensitivity of adipose and muscle tissue to insulin action when compared to wild type controls. Blood pressure was comparable in SHR versus SHR-Plzf+/-, however, there was significant amelioration of cardiomyocyte hypertrophy and cardiac fibrosis in SHR-Plzf+/- rats. Gene expression profiles in the liver and expression of selected genes in the heart revealed differentially expressed genes playing a role in metabolic pathways, PPAR signaling, and cell cycle regulation. These results provide evidence for an important role of Plzf in regulation of metabolic and cardiac traits in the rat and suggest a cross-talk between cell cycle regulators, metabolism, cardiac hypertrophy and fibrosis.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-MTAB-3831
refinement:
raw
dateSubmitted:
07-18-2014
keywords:
functional genomics
dateModified:
12-28-2016
availability:
available
types:
gene expression
name:
Rattus norvegicus
name:
genetic modification design
ID:
A-AFFY-160
name:
Affymetrix GeneChip Rat Gene 1.0 ST Array [RaGene-1_0-st-v1]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-MTAB-3831/E-MTAB-3831.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-MTAB-3831/E-MTAB-3831.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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