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.

Autor: Ritter ML; 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.), Neuroscience Research Center, Medical College of Wisconsin, Milwaukee., Deng G; Medical College of Wisconsin, Milwaukee. Department of Pharmacology and Neuroscience (G.D., Y.D., S.A.S., H.C.), University of Iowa, Iowa City., Reho JJ; 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.), Neuroscience Research Center, Medical College of Wisconsin, Milwaukee.; Comprehensive Rodent Metabolic Phenotyping Core (J.J.R., J.L.G.), Neuroscience Research Center, Medical College of Wisconsin, Milwaukee., Deng Y; Medical College of Wisconsin, Milwaukee. Department of Pharmacology and Neuroscience (G.D., Y.D., S.A.S., H.C.), University of Iowa, Iowa City., Sapouckey SA; Medical College of Wisconsin, Milwaukee. Department of Pharmacology and Neuroscience (G.D., Y.D., S.A.S., H.C.), University of Iowa, Iowa City., Opichka MA; 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.), Neuroscience Research Center, Medical College of Wisconsin, Milwaukee., Balapattabi K; 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.), Neuroscience Research Center, Medical College of Wisconsin, Milwaukee., Wackman KK; 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.), Neuroscience Research Center, Medical College of Wisconsin, Milwaukee., Brozoski DT; 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.), Neuroscience Research Center, Medical College of Wisconsin, Milwaukee., Lu KT; 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.), Neuroscience Research Center, Medical College of Wisconsin, Milwaukee., Paradee WJ; Genome Editing Core Facility (W.J.P.), University of Iowa, Iowa City., Gibson-Corley KN; Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN (K.N.G.-C.)., Cui H; Medical College of Wisconsin, Milwaukee. Department of Pharmacology and Neuroscience (G.D., Y.D., S.A.S., H.C.), University of Iowa, Iowa City., Nakagawa P; 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.), Neuroscience Research Center, Medical College of Wisconsin, Milwaukee.; Cardiovascular Center (P.N., C.D.S., J.L.G.), Neuroscience Research Center, Medical College of Wisconsin, Milwaukee., Morselli LL; Department of Medicine, Division of Endocrinology (L.L.M.), Neuroscience Research Center, Medical College of Wisconsin, Milwaukee., Sigmund CD; 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.), Neuroscience Research Center, Medical College of Wisconsin, Milwaukee.; Cardiovascular Center (P.N., C.D.S., J.L.G.), Neuroscience Research Center, Medical College of Wisconsin, Milwaukee.; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee (C.D.S., J.L.G.)., Grobe JL; 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.), Neuroscience Research Center, Medical College of Wisconsin, Milwaukee.; Comprehensive Rodent Metabolic Phenotyping Core (J.J.R., J.L.G.), Neuroscience Research Center, Medical College of Wisconsin, Milwaukee.; Cardiovascular Center (P.N., C.D.S., J.L.G.), Neuroscience Research Center, Medical College of Wisconsin, Milwaukee.; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee (C.D.S., J.L.G.).; Department of Biomedical Engineering (J.L.G.), University of Iowa, Iowa City.
Jazyk: angličtina
Zdroj: Hypertension (Dallas, Tex. : 1979) [Hypertension] 2022 Dec; Vol. 79 (12), pp. 2843-2853. Date of Electronic Publication: 2022 Oct 19.
DOI: 10.1161/HYPERTENSIONAHA.122.20169
Abstrakt: 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 (Rgs2 Null ) exhibit hypertension, anxiety, and altered adipose development and function.
Methods: To study cell-specific functions of RGS2, a novel gene-targeted mouse harboring a conditional allele for the Rgs2 gene ( Rgs2 Flox ) 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 (Rgs2 Agrp-KO ), or a novel transgenic mouse expressing Cre-recombinase via the ANG (angiotensin) type 1A receptor ( Agtr1a / AT 1A ) promoter encoded in a bacterial artificial chromosome (BAC-AT 1A -Cre) to delete Rgs2 in all Agtr1a -expressing cells ( Rgs2 AT1A-KO ).
Results: Whereas Rgs2 Flox , Rgs2 Agrp-KO , and BAC-AT 1A -Cre mice exhibited normal growth and survival, Rgs2 AT1A-KO exhibited pre-weaning lethality. Relative to littermates, Rgs2 Agrp-KO exhibited reduced fat gains when maintained on a high fat diet, associated with increased energy expenditure. Similarly, surviving adult Rgs2 AT1A-KO mice also exhibited increased energy expenditure. Surprisingly, given the hypertensive phenotype previously reported for Rgs2 Null mice and evidence supporting a role for RGS2 in terminating AT 1A signaling in various cell types, Rgs2 AT1A-KO mice exhibited normal blood pressure, ingestive behaviors, and renal functions, both before and after chronic infusion of ANG (490 ng/kg/min, sc).
Conclusions: These 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.
Databáze: MEDLINE
Externí odkaz: