ArticleThe pharmacogenomics journal2011
Systematic generation of in vivo G protein-coupled receptor mutants in the rat.
Article in The pharmacogenomics journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes.Journal of biomedical science · 2020Review
- Genetic variants help define the role of the MC4R C-terminus in signaling and cell surface stability.Scientific reports · 2018Article
- Towards trans-diagnostic mechanisms in psychiatry: neurobehavioral profile of rats with a loss-of-function point mutation in the dopamine transporter gene.Disease models & mechanisms · 2017Article
- Adult Lysophosphatidic Acid Receptor 1-Deficient Rats with Hyperoxia-Induced Neonatal Chronic Lung Disease Are Protected against Lipopolysaccharide-Induced Acute Lung Injury.Frontiers in physiology · 2017Article
- Effects of Melanocortin 3 and 4 Receptor Deficiency on Energy Homeostasis in Rats.Scientific reports · 2016Article
- Deficiency or inhibition of lysophosphatidic acid receptor 1 protects against hyperoxia-induced lung injury in neonatal rats.Acta physiologica (Oxford, England) · 2016Article
- Enhanced Functional Activity of the Cannabinoid Type-1 Receptor Mediates Adolescent Behavior.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- LPA receptor signaling: pharmacology, physiology, and pathophysiology.Journal of lipid research · 2014Review
- Vascular effects of deletion of melanocortin-4 receptors in rats.Physiological reports · 2013Article
- Melanocortin receptor 4 deficiency affects body weight regulation, grooming behavior, and substrate preference in the rat.Obesity (Silver Spring, Md.) · 2012Article
- Phylomedicine: an evolutionary telescope to explore and diagnose the universe of disease mutations.Trends in genetics : TIG · 2011Review
- G protein-coupled receptors: mutations and endocrine diseases.Nature reviews. Endocrinology · 2011Review
- Rat traps: filling the toolbox for manipulating the rat genome.Genome biology · 2010Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
G-protein-coupled receptors (GPCRs) constitute a large family of cell surface receptors that are involved in a wide range of physiological and pathological processes, and are targets for many therapeutic interventions. However, genetic models in the rat, one of the most widely used model organisms in physiological and pharmacological research, are largely lacking. Here, we applied N-ethyl-N-nitrosourea (ENU)-driven target-selected mutagenesis to generate an in vivo GPCR mutant collection in the rat. A pre-selected panel of 250 human GPCR homologs was screened for mutations in 813 rats, resulting in the identification of 131 non-synonymous mutations. From these, seven novel potential rat gene knockouts were established as well as 45 lines carrying missense mutations in various genes associated with or involved in human diseases. We provide extensive in silico modeling results of the missense mutations and show experimental data, suggesting loss-of-function phenotypes for several models, including Mc4r and Lpar1. Taken together, the approach used resulted not only in a set of novel gene knockouts, but also in allelic series of more subtle amino acid variants, similar as commonly observed in human disease. The mutants presented here may greatly benefit studies to understand specific GPCR function and support the development of novel therapeutic strategies.
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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.