title: Dopamine pathway imbalance in mice lacking Magel2, a Prader-Willi syndrome candidate gene.
abstract: The etiology of abnormal eating behaviors, including binge-eating disorder, is poorly understood. The neural circuits modulating the activities of the neurotransmitters dopamine and serotonin are proposed to be dysfunctional in individuals suffering from eating disorders. Prader-Willi syndrome is a neurodevelopmental disorder that causes extreme food seeking and binge-eating behaviors together with reduced satiety. One of the genes implicated in Prader-Willi syndrome, Magel2, is highly expressed in the regions of the brain that control appetite. Our objective was to examine behaviors relevant to feeding and the neural circuits controlling feeding in a mouse model of Prader-Willi syndrome that lacks expression of the Magel2 gene. We performed behavioral tests related to dopaminergic function, measuring cocaine-induced hyperlocomotion, binge eating, and saccharin-induced anhedonia in Magel2-deficient mice. Next, we analyzed dopaminergic neurons in various brain regions and compared these findings between genotypes. Finally, we examined biochemical markers in the brain under standard diet, high-fat diet, and withdrawal from a high-fat diet conditions. We identified abnormal behaviors and biomarkers reflecting dopaminergic dysfunction in mice lacking Magel2. Our results provide a biological framework for clinical studies of dopaminergic function in children with Prader-Willi syndrome, and may also provide insight into binge-eating disorders that occur in the general population. (PsycINFO Database Record
authors.affiliation: Department of Medical Genetics.
authors.forename: Chloe
authors.initials: C
authors.lastname: Luck
authors.affiliation: Department of Neurobiology, Center for Sleep and Circadian Biology, Northwestern University.
authors.forename: Martha H
authors.initials: MH
authors.lastname: Vitaterna
authors.affiliation: Department of Medical Genetics.
authors.forename: Rachel
authors.initials: R
authors.lastname: Wevrick
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D056912:Binge-Eating Disorder / Q000503:physiopathology; D001921:Brain / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004298:Dopamine / Q000235:genetics* / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011218:Prader-Willi Syndrome / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012701:Serotonin / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D064267:Intrinsically Disordered Proteins
chemical_list: D000951:Antigens, Neoplasm; D004298:Dopamine; D011506:Proteins; D012701:Serotonin; C403091:Magel2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D064267:Intrinsically Disordered Proteins