missense mutation in the non-neural G-protein α-subunit isoforms modulates susceptibility to obesity

• Published in: International Journal of Obesity 2009-05, Vol.33 (5), p.507-518
• Main Authors: Kelly, M.L, Moir, L, Jones, L, Whitehill, E, Anstee, Q.M, Goldin, R.D, Hough, A, Cheeseman, M, Jansson, J.O, Peters, J, Cox, R.D
• Format: Article
• Language: English
• Subjects: alleles; animal models; Animal models in research; Animals; Biological and medical sciences; Biomarkers - blood; Body Composition; Chromogranins; Development and progression; Dietary Fats - administration & dosage; Disease Models, Animal; disease resistance; Disease susceptibility; Energy Metabolism - genetics; Epidemiology; experimental diets; Fysiologi; G proteins; Gene mutations; Genetic aspects; GTP-Binding Protein alpha Subunits - genetics; GTP-Binding Protein alpha Subunits, Gs - genetics; Health Promotion and Disease Prevention; Hyperglycemia - genetics; Internal Medicine; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Mice; missense mutation; Mutation, Missense - genetics; Obesity; Obesity - genetics; original-article; phenotype; Physiological aspects; Physiology; Point Mutation - genetics; Protein Isoforms; protein synthesis; Public Health; transcription (genetics)
• ISSN: 0307-0565; 1476-5497; 1476-5497
• DOI: 10.1038/ijo.2009.30

Objective: The Gnas transcription unit located within an imprinting region encodes several proteins, including the G-protein α-subunit, Gsα, its isoform XLαs and their variant truncated neural forms GsαN1 and XLN1. Gsα and GsαN1 are expressed predominantly from the maternally derived allele in some tissues, whereas XLαs and XLN1 are expressed exclusively from the paternally derived allele. The relative contribution of full-length Gsα and XLαs, and truncated forms GsαN1 and XLN1 to phenotype is unknown. The edematous-small point mutation (Oed-Sml) in exon 6 of Gnas lies downstream of GsαN1 and XLN1, but affects full-length Gsα and XLαs, allowing us to address the role of full-length Gs and XLs. The aim of this study was therefore to determine the metabolic phenotypes of Oed and Sml mice, and to correlate phenotypes with affected transcripts.