title: Regionally reduced brain volume, altered serotonin neurochemistry, and abnormal behavior in mice null for the circadian rhythm output gene Magel2.
abstract: Magel2 belongs to the MAGE/necdin family of proteins, which have roles in cell cycle, differentiation, and apoptosis. The Magel2 gene is expressed in various brain regions, most notably the hypothalamus. Mice with a targeted deletion of Magel2 display hypoactivity, blunted circadian rhythm, decreased fertility, and increased adiposity. The human ortholog, MAGEL2, is one of a set of paternally expressed, imprinted genes inactivated in most cases of Prader-Willi syndrome, a complex neurodevelopmental disorder. To explore the role of Magel2, brain morphology, brain neurochemistry, and behavior were measured in Magel2-null mice. Brain volume was reduced in specific regions, particularly in the parieto-temporal lobe of the cerebral cortex, the amygdala, the hippocampus, and the nucleus accumbens, as measured by quantitative magnetic resonance imaging. Abnormal neurochemistry was detected in brain samples from adult mice, consisting of decreased serotonin and 5-hydroxyindoleacetic acid in the cortex and the hypothalamus, and decreased dopamine in the hypothalamus. Magel2-null mice displayed relatively normal motor and learning abilities, but exhibited abnormal behavior in novel environments. This study lends support to the important role of the circadian rhythm output gene Magel2 in brain structure and behavior.
authors.affiliation: Department of Medical Genetics, University of Alberta, Edmonton, Canada.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Mercer
authors.forename: Erin M
authors.initials: EM
authors.lastname: Kwolek
authors.forename: Jocelyn M
authors.initials: JM
authors.lastname: Bischof
authors.forename: Matthijs
authors.initials: M
authors.lastname: van Eede
authors.forename: R Mark
authors.initials: RM
authors.lastname: Henkelman
authors.forename: Rachel
authors.initials: R
authors.lastname: Wevrick
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry; D002940:Circadian Rhythm / Q000235:genetics; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D008279:Magnetic Resonance Imaging; D051379:Mice; D018345:Mice, Knockout; D009448:Neurochemistry; D009929:Organ Size; D011506:Proteins / Q000235:genetics*; D012701:Serotonin / Q000032:analysis*; D047908:Intracellular Signaling Peptides and Proteins; D064267:Intrinsically Disordered Proteins
chemical_list: D000951:Antigens, Neoplasm; D006897:Hydroxyindoleacetic Acid; D011506:Proteins; D012701:Serotonin; C403091:Magel2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D064267:Intrinsically Disordered Proteins