MAGEL2 is one of five genes in the Prader-Willi syndrome (PWS) critical domain on chromosome 15 that encodes a protein. Our group recently described a group of patients with mutations of MAGEL2 causing Prader-Willi features and autism. Autism spectrum disorder is seen in up to one third of individuals with PWS, and in all individuals with MAGEL2 mutations reported to date. Mice lacking the Magel2 gene have been generated, but have not been examined for autism-like behaviors. We hypothesize that those mice may have deficits of social interaction, and other autism-like behaviors. We propose a comprehensive battery of experiments to test for altered social interaction, repetitive behaviors, and learning impairment in mice lacking the Magel2 gene. Both male and female mice will be assessed, and they will be compared to their genetically normal siblings. The in-depth behavioral examination of animal models of PWS is of critical importance, as the field is in desperate need of reproducible outcome measures that could be used in future drug trials aiming to treat symptoms of PWS.
Magel2 knockout mice manifest altered social phenotypes and a deficit in preference for social novelty. Fountain MD, Tao H, Chen CA, Yin J, Schaaf CP. Genes, Brain and Behavior. 2017 Jul;16(6):592-600.
USP7 Acts as a Molecular Rheostat to Promote WASH-Dependent Endosomal Protein Recycling and Is Mutated in a Human Neurodevelopmental Disorder. Hao YH, Fountain MD Jr, Fon Tacer K, Xia F, Bi W, Kang SH, Patel A, Rosenfeld JA, Le Caignec C, Isidor B, Krantz ID, Noon SE, Pfotenhauer JP, Morgan TM, Moran R, Pedersen RC, Saenz MS, Schaaf CP, Potts PR. Molecular Cell. 2015 Sep 17;59(6):956-69.
MAGEL2 and Oxytocin-Implications in Prader-Willi Syndrome and Beyond. Fountain MD Jr, Schaaf CP. Biological Psychiatry. 2015 Jul 15;78(2):78-80.
Christian Schaaf, M.D, Ph.D.
Baylor College of Medicine