Cardiometabolic Consequences of Deleting the Regulator of G protein Signaling-2 () From Cells Expressing Agouti-Related Peptide or the ANG (Angiotensin) II Type 1A Receptor in Mice.

BACKGROUND

RGS (regulator of G protein signaling) family members catalyze the termination of G protein signaling cascades. Single nucleotide polymorphisms in the gene in humans have been linked to hypertension, preeclampsia, and anxiety disorders. Mice deficient for ) 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 gene () was developed. These mice were bred with mice expressing Cre-recombinase via the Agouti-related peptide locus (-Cre) to cause deletion of from all cells expressing ), or a novel transgenic mouse expressing Cre-recombinase via the ANG (angiotensin) type 1A receptor (/ AT) promoter encoded in a bacterial artificial chromosome (BAC-AT-Cre) to delete in all -expressing cells ().

RESULTS

Whereas , , and BAC-AT-Cre mice exhibited normal growth and survival, exhibited pre-weaning lethality. Relative to littermates, exhibited reduced fat gains when maintained on a high fat diet, associated with increased energy expenditure. Similarly, surviving adult mice also exhibited increased energy expenditure. Surprisingly, given the hypertensive phenotype previously reported for mice and evidence supporting a role for RGS2 in terminating AT signaling in various cell types, 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 and illustrate the role of within selected cell types for cardiometabolic control.