Journal article
Cardiometabolic Consequences of Deleting the Regulator of G protein Signaling-2 (Rgs2) From Cells Expressing Agouti-Related Peptide or the ANG (Angiotensin) II Type 1A Receptor in Mice
Hypertension (Dallas, Tex. 1979), Vol.79(12), pp.2843-2853
10/19/2022
DOI: 10.1161/HYPERTENSIONAHA.122.20169
PMCID: PMC9649888
PMID: 36259376
Abstract
BACKGROUND RGS (regulator of G protein signaling) family members catalyze the termination of G protein signaling cascades. Single nucleotide polymorphisms in the RGS2 gene in humans have been linked to hypertension, preeclampsia, and anxiety disorders. Mice deficient for Rgs2 (Rgs2Null) exhibit hypertension, anxiety, and altered adipose development and function. METHODSTo study cell-specific functions of RGS2, a novel gene-targeted mouse harboring a conditional allele for the Rgs2 gene (Rgs2Flox) was developed. These mice were bred with mice expressing Cre-recombinase via the Agouti-related peptide locus (Agrp-Cre) to cause deletion of Rgs2 from all cells expressing Agrp (Rgs2Agrp-KO), or a novel transgenic mouse expressing Cre-recombinase via the ANG (angiotensin) type 1A receptor (Agtr1a/ AT1A) promoter encoded in a bacterial artificial chromosome (BAC-AT1A-Cre) to delete Rgs2 in all Agtr1a-expressing cells (Rgs2AT1A-KO). RESULTSWhereas Rgs2Flox, Rgs2Agrp-KO, and BAC-AT1A-Cre mice exhibited normal growth and survival, Rgs2AT1A-KO exhibited pre-weaning lethality. Relative to littermates, Rgs2Agrp-KO exhibited reduced fat gains when maintained on a high fat diet, associated with increased energy expenditure. Similarly, surviving adult Rgs2AT1A-KO mice also exhibited increased energy expenditure. Surprisingly, given the hypertensive phenotype previously reported for Rgs2Null mice and evidence supporting a role for RGS2 in terminating AT1A signaling in various cell types, Rgs2AT1A-KO mice exhibited normal blood pressure, ingestive behaviors, and renal functions, both before and after chronic infusion of ANG (490 ng/kg/min, sc). CONCLUSIONSThese results demonstrate the development of a novel mouse with conditional expression of Rgs2 and illustrate the role of Rgs2 within selected cell types for cardiometabolic control.
Details
- Title: Subtitle
- Cardiometabolic Consequences of Deleting the Regulator of G protein Signaling-2 (Rgs2) From Cells Expressing Agouti-Related Peptide or the ANG (Angiotensin) II Type 1A Receptor in Mice
- Creators
- McKenzie L Ritter - Medical College of WisconsinGuorui Deng - University of IowaJohn J Reho - Medical College of WisconsinYue Deng - University of IowaSarah A Sapouckey - University of IowaMegan A Opichka - Department of Physiology (M.L.R., J.J.R., M.A.O., K.B., K.K.W., D.T.B., K.-T.L., P.N., C.D.S., J.L.G.)Kirthikaa Balapattabi - Medical College of WisconsinKelsey K Wackman - Medical College of WisconsinDaniel T Brozoski - Medical College of WisconsinKo-Ting Lu - Department of Physiology (M.L.R., J.J.R., M.A.O., K.B., K.K.W., D.T.B., K.-T.L., P.N., C.D.S., J.L.G.)William J Paradee - University of IowaKatherine N Gibson-Corley - Vanderbilt UniversityHuxing Cui - University of IowaPablo Nakagawa - Medical College of WisconsinLisa L Morselli - Medical College of WisconsinCurt D Sigmund - Medical College of WisconsinJustin L Grobe - Medical College of Wisconsin
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.79(12), pp.2843-2853
- DOI
- 10.1161/HYPERTENSIONAHA.122.20169
- PMID
- 36259376
- PMCID
- PMC9649888
- NLM abbreviation
- Hypertension
- eISSN
- 1524-4563
- Language
- English
- Date published
- 10/19/2022
- Academic Unit
- Molecular Physiology and Biophysics; The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; UI Research Foundation; Neuroscience and Pharmacology; Medicine Administration; Internal Medicine
- Record Identifier
- 9984306742402771
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