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.

Disease Annotations    
Dysbiosis  (IMP,ISO)

Gene Ontology Annotations    

Biological Process
vasodilation  (IMP)

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)

SS-Gper1em1Bj-/-  (NA)

Additional Information