ArticleInternational journal of obesity (2005)2019
Development and initial characterization of a novel ghrelin receptor CRISPR/Cas9 knockout wistar rat model.
Article in International journal of obesity (2005), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- A closer look at alcohol-induced changes in the ghrelin system: novel insights from preclinical and clinical data.Addiction biology · 2022Trial
- Trial
- Reduced plasma ghrelin concentrations are associated with decreased brain reactivity to food cues after laparoscopic sleeve gastrectomy.Psychoneuroendocrinology · 2019Trial
- A Dimer for Dinner: The Impact of GHS-R1a Heterodimerization on Feeding Circuits.Biomolecules · 2026Review
- Characterizing ghrelin's role in dysregulating GLP-1-mediated function and promoting the development of alcohol-associated liver disease.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Chemoarchitectural studies of the rat hypothalamus and zona incerta.bioRxiv : the preprint server for biology · 2025Article
- Genetic or pharmacological GHSR blockade has sexually dimorphic effects in rodents on a high-fat diet.Communications biology · 2024Article
- Role of ghrelin hormone in the development of alcohol-associated liver disease.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Genetic or pharmacological GHSR blockade has sexually dimorphic effects in rodents on a high-fat diet.Research square · 2023Article
- Intermittent-access operant alcohol self-administration promotes binge-like drinking and drinking despite negative consequences in male and female heterogeneous stock rats.Neuropharmacology · 2023Article
- Initial Pharmacological Characterization of a Major Hydroxy Metabolite of PF-5190457: Inverse Agonist Activity of PF-6870961 at the Ghrelin Receptor.The Journal of pharmacology and experimental therapeutics · 2023Article
- Ghrelin receptor antagonist JMV2959 blunts cocaine and oxycodone drug-seeking, but not self-administration, in male rats.Frontiers in pharmacology · 2023Article
- Complexes of Ghrelin GHS-R1a, GHS-R1b, and Dopamine DThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Advances in Genome Editing and Application to the Generation of Genetically Modified Rat Models.Frontiers in genetics · 2021Review
- Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes.Journal of biomedical science · 2020Review
- Cas9 Ribonucleoprotein Complex Delivery: Methods and Applications for Neuroinflammation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2019Review
- Opioid Addiction, Genetic Susceptibility, and Medical Treatments: A Review.International journal of molecular sciences · 2019Review
- Reply to "Letter to Editor: Chronic alcohol exposure alters circulating insulin and ghrelin levels in hepatic steatosis: a translational research perspective".American journal of physiology. Gastrointestinal and liver physiology · 2019Article
- Ghrelin receptor deletion reduces binge-like alcohol drinking in rats.Journal of neuroendocrinology · 2019Article
- Rat Models of Metabolic Syndrome.Methods in molecular biology (Clifton, N.J.) · 2019Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND/
objectivesGhrelin, a stomach-derived hormone implicated in numerous behaviors including feeding, reward, stress, and addictive behaviors, acts by binding to the growth hormone secretagogue receptor (GHSR). Here, we present the development, verification, and initial characterization of a novel GHSR knockout (KO) Wistar rat model created with CRISPR genome editing.
methodsUsing CRISPR/Cas9, we developed a GHSR KO in a Wistar background. Loss of GHSR mRNA expression was histologically verified using RNAscope in wild-type (WT; n = 2) and KO (n = 2) rats. We tested the effects of intraperitoneal acyl-ghrelin administration on food consumption and plasma growth hormone (GH) concentrations in WT (n = 8) and KO (n = 8) rats. We also analyzed locomotion, food consumption, and body fat composition in these animals. Body weight was monitored from early development to adulthood.
resultsThe RNAscope analysis revealed an abundance of GHSR mRNA expression in the hypothalamus, midbrain, and hippocampus in WTs, and no observed probe binding in KOs. Ghrelin administration increased plasma GH levels (p = 0.0067) and food consumption (p = 0.0448) in WT rats but not KOs. KO rats consumed less food overall at basal conditions and weighed significantly less compared with WTs throughout development (p = 0.0001). Compared with WTs, KOs presented higher concentrations of brown adipose tissue (BAT; p = 0.0322).
conclusionsWe have verified GHSR deletion in our KO model using histological, physiological, neuroendocrinological, and behavioral measures. Our findings indicate that GHSR deletion in rats is not only associated with a lack of response to ghrelin, but also associated with decreases in daily food consumption and body growth, and increases in BAT. This GHSR KO Wistar rat model provides a novel tool for studying the role of the ghrelin system in obesity and in a wide range of medical and neuropsychiatric disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.