RGD Reference Report - Attenuation of Microbiotal Dysbiosis and Hypertension in a CRISPR/Cas9 Gene Ablation Rat Model of GPER1. - Rat Genome Database

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Attenuation of Microbiotal Dysbiosis and Hypertension in a CRISPR/Cas9 Gene Ablation Rat Model of GPER1.

Authors: Waghulde, Harshal  Cheng, Xi  Galla, Sarah  Mell, Blair  Cai, Jingwei  Pruett-Miller, Shondra M  Vazquez, Guillermo  Patterson, Andrew  Vijay Kumar, Matam  Joe, Bina 
Citation: Waghulde H, etal., Hypertension. 2018 Nov;72(5):1125-1132. doi: 10.1161/HYPERTENSIONAHA.118.11175.
RGD ID: 39939000
Pubmed: PMID:30354811   (View Abstract at PubMed)
PMCID: PMC6208154   (View Article at PubMed Central)
DOI: DOI:10.1161/HYPERTENSIONAHA.118.11175   (Journal Full-text)

G-protein-coupled estrogen receptor, Gper1, has been implicated in cardiovascular disease, but its mechanistic role in blood pressure control is poorly understood. Here, we demonstrate that genetically salt-sensitive hypertensive rats with complete genomic excision of Gper1 by a multiplexed guide RNA CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 (CRISPR associated proteins) approach present with lower blood pressure, which was accompanied by altered microbiota, different levels of circulating short chain fatty acids, and improved vascular relaxation. Microbiotal transplantation from hypertensive Gper1+/+ rats reversed the cardiovascular protective effect exerted by the genomic deletion of Gper1. Thus, this study reveals a role for Gper1 in promoting microbiotal alterations that contribute to cardiovascular pathology. However, the exact mechanism by which Gper1 regulates blood pressure is still unknown. Our results indicate that the function of Gper1 is contextually dependent on the microbiome, whereby, contemplation of using Gper1 as a target for therapy of cardiovascular disease requires caution.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GPER1HumanDysbiosis amelioratesISOGper1 (Rattus norvegicus) RGD 
Gper1RatDysbiosis amelioratesIMP  RGD 
Gper1MouseDysbiosis amelioratesISOGper1 (Rattus norvegicus) RGD 
Gper1em1BjRatDysbiosis amelioratesIMP  RGD 
SS-Gper1em1Bj-/-RatDysbiosis amelioratesIMP  RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Gper1Ratvasodilation  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Gper1Ratabnormal free fatty acids level  IMP compared to wild type SS ratRGD 
Gper1em1BjRatabnormal free fatty acids level  IMP compared to wild type SS ratRGD 
SS-Gper1em1Bj-/-Ratabnormal free fatty acids level  IMP compared to wild type SS ratRGD 
Gper1Ratdecreased mean systemic arterial blood pressure  IMP compared to wild type SS ratRGD 
Gper1em1BjRatdecreased mean systemic arterial blood pressure  IMP compared to wild type SS ratRGD 
SS-Gper1em1Bj-/-Ratdecreased mean systemic arterial blood pressure  IMP compared to wild type SS ratRGD 
Gper1Ratdecreased pulse pressure  IMP compared to wild type SS ratRGD 
Gper1em1BjRatdecreased pulse pressure  IMP compared to wild type SS ratRGD 
SS-Gper1em1Bj-/-Ratdecreased pulse pressure  IMP compared to wild type SS ratRGD 
Gper1Ratdecreased systemic arterial diastolic blood pressure  IMP compared to wild type SS ratRGD 
Gper1em1BjRatdecreased systemic arterial diastolic blood pressure  IMP compared to wild type SS ratRGD 
SS-Gper1em1Bj-/-Ratdecreased systemic arterial diastolic blood pressure  IMP compared to wild type SS ratRGD 
Gper1Ratdecreased systemic arterial systolic blood pressure  IMP compared to wild type SS ratRGD 
Gper1em1BjRatdecreased systemic arterial systolic blood pressure  IMP compared to wild type SS ratRGD 
SS-Gper1em1Bj-/-Ratdecreased systemic arterial systolic blood pressure  IMP compared to wild type SS ratRGD 
Gper1Ratincreased body length  IMP compared to wild type SS ratRGD 
Gper1em1BjRatincreased body length  IMP compared to wild type SS ratRGD 
SS-Gper1em1Bj-/-Ratincreased body length  IMP compared to wild type SS ratRGD 
Gper1Ratincreased body weight  IMP compared to wild type SS ratRGD 
Gper1em1BjRatincreased body weight  IMP compared to wild type SS ratRGD 
SS-Gper1em1Bj-/-Ratincreased body weight  IMP compared to wild type SS ratRGD 
Gper1Ratincreased vasodilation  IMP compared to wild type SS ratRGD 
Gper1em1BjRatincreased vasodilation  IMP compared to wild type SS ratRGD 
SS-Gper1em1Bj-/-Ratincreased vasodilation  IMP compared to wild type SS ratRGD 
Objects Annotated

Genes (Rattus norvegicus)
Gper1  (G protein-coupled estrogen receptor 1)
Gper1em1Bj  (G protein-coupled estrogen receptor 1; CRISPR/Cas 9 induced mutant 1, Bj)

Genes (Mus musculus)
Gper1  (G protein-coupled estrogen receptor 1)

Genes (Homo sapiens)
GPER1  (G protein-coupled estrogen receptor 1)

Strains
SS-Gper1em1Bj-/-  (NA)


Additional Information