RGD Reference Report - Downregulation of Plzf Gene Ameliorates Metabolic and Cardiac Traits in the Spontaneously Hypertensive Rat. - Rat Genome Database

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Downregulation of Plzf Gene Ameliorates Metabolic and Cardiac Traits in the Spontaneously Hypertensive Rat.

Authors: Liška, František  Landa, Vladimír  Zídek, Václav  Mlejnek, Petr  Šilhavý, Jan  Šimáková, Miroslava  Strnad, Hynek  Trnovská, Jaroslava  Škop, Vojtěch  Kazdová, Ludmila  Starker, Colby G  Voytas, Daniel F  Izsvák, Zsuzsanna  Mancini, Massimiliano  Šeda, Ondřej  Křen, Vladimír  Pravenec, Michal 
Citation: Liška F, etal., Hypertension. 2017 Jun;69(6):1084-1091. doi: 10.1161/HYPERTENSIONAHA.116.08798. Epub 2017 Apr 10.
RGD ID: 150340623
Pubmed: PMID:28396530   (View Abstract at PubMed)
DOI: DOI:10.1161/HYPERTENSIONAHA.116.08798   (Journal Full-text)

The spontaneously hypertensive rat (SHR), one of the most widely used model of essential hypertension, is predisposed to left ventricular hypertrophy, myocardial fibrosis, and metabolic disturbances. Recently, quantitative trait loci influencing blood pressure, left ventricular mass, and heart interstitial fibrosis were genetically isolated within a minimal congenic subline that contains only 7 genes, including mutant Plzf (promyelocytic leukemia zinc finger) candidate gene. To identify Plzf as a quantitative trait gene, we targeted Plzf in the SHR using the transcription activator-like effector nuclease technique and obtained SHR line harboring targeted Plzf gene with a premature stop codon. Because the Plzf targeted allele is semilethal, morphologically normal heterozygous rats 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 with 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 that play a role in metabolic pathways, PPAR (peroxisome proliferator-activated receptor) 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.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SHR-Zbtb16em1Ipcv+/-Ratcardiac interstitial fibrosis amelioratesIMP  RGD 
Zbtb16Ratcardiac interstitial fibrosis amelioratesIMP  RGD 
Zbtb16em1IpcvRatcardiac interstitial fibrosis amelioratesIMP  RGD 
SHR-Zbtb16em1Ipcv+/-Ratdecreased body weight  IMP compared to wild type SHR/OlaIpcvRGD 
Zbtb16Ratdecreased body weight  IMP compared to wild type SHR/OlaIpcvRGD 
Zbtb16em1IpcvRatdecreased body weight  IMP compared to wild type SHR/OlaIpcvRGD 
SHR-Zbtb16em1Ipcv+/-Ratdecreased circulating cholesterol level  IMP compared to wild type SHR/OlaIpcvRGD 
Zbtb16Ratdecreased circulating cholesterol level  IMP compared to wild type SHR/OlaIpcvRGD 
Zbtb16em1IpcvRatdecreased circulating cholesterol level  IMP compared to wild type SHR/OlaIpcvRGD 
SHR-Zbtb16em1Ipcv+/-Ratdecreased circulating triglyceride level  IMP compared to wild type SHR/OlaIpcvRGD 
Zbtb16Ratdecreased circulating triglyceride level  IMP compared to wild type SHR/OlaIpcvRGD 
Zbtb16em1IpcvRatdecreased circulating triglyceride level  IMP compared to wild type SHR/OlaIpcvRGD 
SHR-Zbtb16em1Ipcv+/-Ratdecreased epididymal fat pad weight  IMP compared to wild type SHR/OlaIpcvRGD 
Zbtb16Ratdecreased epididymal fat pad weight  IMP compared to wild type SHR/OlaIpcvRGD 
Zbtb16em1IpcvRatdecreased epididymal fat pad weight  IMP compared to wild type SHR/OlaIpcvRGD 
SHR-Zbtb16em1Ipcv+/-Ratdecreased liver cholesterol level  IMP compared to wild type SHR/OlaIpcvRGD 
Zbtb16Ratdecreased liver cholesterol level  IMP compared to wild type SHR/OlaIpcvRGD 
Zbtb16em1IpcvRatdecreased liver cholesterol level  IMP compared to wild type SHR/OlaIpcvRGD 
SHR-Zbtb16em1Ipcv+/-Ratdecreased liver triglyceride level  IMP compared to wild type SHR/OlaIpcvRGD 
Zbtb16Ratdecreased liver triglyceride level  IMP compared to wild type SHR/OlaIpcvRGD 
Zbtb16em1IpcvRatdecreased liver triglyceride level  IMP compared to wild type SHR/OlaIpcvRGD 
SHR-Zbtb16em1Ipcv+/-Ratdecreased myocardial fiber size  IMP compared to wild type SHR/OlaIpcvRGD 
Zbtb16Ratdecreased myocardial fiber size  IMP compared to wild type SHR/OlaIpcvRGD 
Zbtb16em1IpcvRatdecreased myocardial fiber size  IMP compared to wild type SHR/OlaIpcvRGD 
SHR-Zbtb16em1Ipcv+/-Ratimproved glucose tolerance  IMP compared to wild type SHR/OlaIpcvRGD 
Zbtb16Ratimproved glucose tolerance  IMP compared to wild type SHR/OlaIpcvRGD 
Zbtb16em1IpcvRatimproved glucose tolerance  IMP compared to wild type SHR/OlaIpcvRGD 
SHR-Zbtb16em1Ipcv+/-Ratincreased insulin sensitivity  IMP compared to wild type SHR/OlaIpcvRGD 
Zbtb16Ratincreased insulin sensitivity  IMP compared to wild type SHR/OlaIpcvRGD 
Zbtb16em1IpcvRatincreased insulin sensitivity  IMP compared to wild type SHR/OlaIpcvRGD 
Objects Annotated

Genes (Rattus norvegicus)
Zbtb16  (zinc finger and BTB domain containing 16)
Zbtb16em1Ipcv  (zinc finger and BTB domain containing 16; TALEN induced mutant 1, Ipcv)

Strains
SHR-Zbtb16em1Ipcv+/-  (NA)


Additional Information