title: Mice lacking G0S2 are lean and cold-tolerant.
abstract: G 0/G 1 switch gene 2 (G0S2) is a protein that was first identified in a search for lymphocyte G 0/G 1 switch genes. A direct role for G0S2 in cell cycle regulation has proven elusive. Yet, there is prior evidence for G0S2 functioning in tumor suppression, immune regulation and lipolysis. To explore definitively G0S2 functions, mice lacking G0S2 were generated and characterized. G0S2(-/-) mice were born at a Mendelian ratio and were phenotypically normal, with the exception of a possible lactation defect. G0S2(-/-) female mice carried viable pups to term, but could not typically sustain them beyond 48 h. G0S2 is shown here to be most highly expressed in adipose tissue. It is also expressed in liver, skeletal muscle, lung, ventricles of the heart, and components of the kidney. G0S2 loss significantly decreased relative body weight gain as compared with wild-type (WT) (G0S2(+/+)) mice, with a significant decrease in gonadal fat pad weight and a significant increase in serum glycerol levels. This decreased relative body weight gain is not associated with a significant decrease in food intake or increase in activity of G0S2(-/-) mice. In fact, G0S2(-/-) mice were significantly less active at night than G0S2(+/+) mice. When fed with a high fat diet (45% fat diet), G0S2 loss did not prevent diet-induced obesity in mice. Intriguingly, G0S2 loss improved acute cold tolerance, augmenting expression of genes involved in thermogenesis. In summary, in vivo roles for G0S2 were found in lactation, energy balance, and thermogenesis. This study provides a basis for tumor suppressive effects of G0S2 by regulating lipolysis.
authors.affiliation: Department of Pharmacology and Toxicology; Geisel School of Medicine at Dartmouth; Hanover, NH USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Pharmacology and Toxicology; Geisel School of Medicine at Dartmouth; Hanover, NH USA.
authors.forename: Alexandra G N
authors.initials: AG
authors.lastname: Lopez-Aguiar
authors.affiliation: Department of Physiology and Neurobiology; Geisel School of Medicine at Dartmouth; Hanover, NH USA.
authors.forename: Aihua
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Toxicology; Geisel School of Medicine at Dartmouth; Hanover, NH USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pharmacology and Toxicology; Geisel School of Medicine at Dartmouth; Hanover, NH USA.
authors.forename: David
authors.initials: D
authors.lastname: Sekula
authors.affiliation: Department of Physiology and Neurobiology; Geisel School of Medicine at Dartmouth; Hanover, NH USA.
authors.forename: Eugene E
authors.initials: EE
authors.lastname: Nattie
authors.affiliation: Department of Pharmacology and Toxicology; Geisel School of Medicine at Dartmouth; Hanover, NH USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Freemantle
authors.affiliation: Department of Pharmacology and Toxicology; Geisel School of Medicine at Dartmouth; Hanover, NH USA; Department of Medicine; Geisel School of Medicine at Dartmouth; Hanover, NH USA; Norris Cotton Cancer Center; Dartmouth-Hitchcock Medical Center; Lebanon, NH USA.
authors.forename: Ethan
authors.initials: E
authors.lastname: Dmitrovsky
mesh_terms: D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D003080:Cold Temperature; D004032:Diet; D004435:Eating; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005990:Glycerol / Q000097:blood; D007774:Lactation / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000235:genetics; D009928:Organ Specificity; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D012737:Sex Factors; D022722:Thermogenesis / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D005227:Fatty Acids; C508072:G0S2 protein, mouse; D005990:Glycerol; D010100:Oxygen
keywords: G0S2; body weight; cold tolerance; knockout mice; lactation; metabolism; tumor suppressor