title: Magel2 knockout mice manifest altered social phenotypes and a deficit in preference for social novelty.
abstract: MAGEL2 is one of five protein-coding, maternally imprinted, paternally expressed genes in the Prader-Willi syndrome (PWS)-critical domain on chromosome 15q11-q13. Truncating pathogenic variants of MAGEL2 cause Schaaf-Yang syndrome (SHFYNG) (OMIM #615547), a neurodevelopmental disorder related to PWS. Affected individuals manifest a spectrum of neurocognitive and behavioral phenotypes, including intellectual disability and autism spectrum disorder (ASD). Magel2 knockout mice carrying a maternally inherited, imprinted wild-type (WT) allele and a paternally inherited Magel2-lacZ knock-in allele, which abolishes endogenous Magel2 gene function, exhibit several features reminiscent of the human Prader-Willi phenotypes, including neonatal growth retardation, excessive weight gain after weaning and increased adiposity in adulthood. They were shown to have altered circadian rhythm, reduced motor activity and reduced fertility. An extensive assessment for autism-like behaviors in this mouse model was warranted, because of the high prevalence of ASD in human patients. The behavior of Magel2 knockout mice and their WT littermates were assayed via open field, elevated plus maze, tube, three-chamber and partition tests. Our studies confirm decreased horizontal activity of male and female mice and increased vertical activity of females, in the open field. Both sexes spent more time in the open arm of the elevated plus maze, suggestive of reductions in anxiety. Both sexes displayed a lack of preference for social novelty, via a lack of discrimination between known and novel partners in the partition test. The in-depth investigation of behavioral profiles caused by Magel2 loss-of-function helps to elucidate the etiology of behavioral phenotypes both for SHFYNG and PWS in general.
authors.affiliation: Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Fountain
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.
authors.forename: H
authors.initials: H
authors.lastname: Tao
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.
authors.forename: C-A
authors.initials: CA
authors.lastname: Chen
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Yin
authors.affiliation: Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.
authors.forename: C P
authors.identifier: 0000-0002-2148-7490
authors.initials: CP
authors.lastname: Schaaf
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D005106:Exploratory Behavior; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011218:Prader-Willi Syndrome / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012919:Social Behavior; D047908:Intracellular Signaling Peptides and Proteins; D064267:Intrinsically Disordered Proteins
chemical_list: D000951:Antigens, Neoplasm; D011506:Proteins; C403091:Magel2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D064267:Intrinsically Disordered Proteins
keywords:  ASD;  Magel2;  PWS; 15q11; Prader-Willi syndrome; Schaaf-Yang syndrome; autism; behavior; neurodevelopmental disorder; social behavior