Faculty Collaboration Database

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 2022 Dec;79(12):2843-2853

Date

10/20/2022

Pubmed ID

36259376

Pubmed Central ID

PMC9649888

DOI

10.1161/HYPERTENSIONAHA.122.20169

Scopus ID

2-s2.0-85141891708 (requires institutional sign-in at Scopus site)   1 Citation

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 (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.

Author List

Ritter ML, Deng G, Reho JJ, Deng Y, Sapouckey SA, Opichka MA, Balapattabi K, Wackman KK, Brozoski DT, Lu KT, Paradee WJ, Gibson-Corley KN, Cui H, Nakagawa P, Morselli LL, Sigmund CD, Grobe JL

Authors

Justin L. Grobe PhD Professor in the Physiology department at Medical College of Wisconsin
Lisa Morselli MD, PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
Pablo Nakagawa PhD Assistant Professor in the Physiology department at Medical College of Wisconsin
John J. Reho Research Scientist II in the Physiology department at Medical College of Wisconsin
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Agouti-Related Protein
Animals
Hypertension
Mice
Mice, Knockout
Mice, Transgenic
RGS Proteins
Receptor, Angiotensin, Type 1
Recombinases