title: Association between regulator of G protein signaling 9-2 and body weight.
abstract: Regulator of G protein signaling 9-2 (RGS9-2) is a protein that is highly enriched in the striatum, a brain region that mediates motivation, movement and reward responses. We identified a naturally occurring 5 nucleotide deletion polymorphism in the human RGS9 gene and found that the mean body mass index (BMI) of individuals with the deletion was significantly higher than those without. A splicing reporter minigene assay demonstrated that the deletion had the potential to significantly decrease the levels of correctly spliced RGS9 gene product. We measured the weights of rats after virally transduced overexpression of RGS9-2 or the structurally related RGS proteins, RGS7, or RGS11, in the nucleus accumbens (NAc) and observed a reduction in body weight after overexpression of RGS9-2 but not RGS7 or 11. Conversely, we found that the RGS9 knockout mice were heavier than their wild-type littermates and had significantly higher percentages of abdominal fat. The constituent adipocytes were found to have a mean cross-sectional area that was more than double that of corresponding cells from wild-type mice. However, food intake and locomotion were not significantly different between the two strains. These studies with humans, rats and mice implicate RGS9-2 as a factor in regulating body weight.
authors: Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America.
authors: Jeffrey L
authors: JL
authors: Waugh
authors: Jeremy
authors: J
authors: Celver
authors: Meenakshi
authors: M
authors: Sharma
authors: Robert L
authors: RL
authors: Dufresne
authors: Dimitra
authors: D
authors: Terzi
authors: S Craig
authors: SC
authors: Risch
authors: William G
authors: WG
authors: Fairbrother
authors: Rachael L
authors: RL
authors: Neve
authors: John P
authors: JP
authors: Kane
authors: Mary J
authors: MJ
authors: Malloy
authors: Clive R
authors: CR
authors: Pullinger
authors: Harvest F
authors: HF
authors: Gu
authors: Christos
authors: C
authors: Tsatsanis
authors: Steven P
authors: SP
authors: Hamilton
authors: Stephen J
authors: SJ
authors: Gold
authors: Venetia
authors: V
authors: Zachariou
authors: Abraham
authors: A
authors: Kovoor
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics*; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism / Q000473:pathology; D007438:Introns / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009043:Motor Activity; D009714:Nucleus Accumbens / Q000378:metabolism; D020710:RGS Proteins / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics; D051381:Rats; D017384:Sequence Deletion / Q000235:genetics; D015431:Weight Loss / Q000235:genetics
chemical_list: D020710:RGS Proteins; C116925:regulator of g-protein signaling 9