title: Ube3a expression is not altered in Mecp2 mutant mice.
abstract: Rett syndrome (RTT) is a neurodevelopmental disorder characterized by cognitive regression, loss of purposeful hand movements and speech, stereotypies, ataxia, seizures, mental retardation and acquired microcephaly. Mutations in MECP2, encoding methyl-CpG-binding protein 2, are responsible for approximately 90% of classic RTT cases. RTT displays phenotypic overlap with Angelman syndrome, a disorder caused by loss of expression of the imprinted gene UBE3A. MeCP2 binds to methylated DNA and may alter the expression of imprinted genes, thereby suggesting a mechanistic link between the two disorders. Here, we tested the hypothesis that MeCP2 deficiency affects expression of Ube3a in mouse models of RTT. As Ube3a is only imprinted in brain, we evaluated Ube3a expression in brains of 15 different litters of neonatal or 8-week-old male Mecp2 mutant mice by real-time quantitative RT-PCR and western blot analysis. We found no significant differences between Mecp2(tm1.1Bird/Y) or Mecp2(tm1.1Jae/Y) mutants and their wild-type male siblings that served as negative controls. In positive control mice carrying a maternally inherited Ube3a deletion, Ube3a sense transcript and protein levels were drastically reduced. Our data contrast with two recent reports of substantially decreased Ube3a expression in brain tissues of MeCP2-deficient mice. We, therefore, challenge the conclusion that decreased UBE3A/Ube3a expression contributes to the pathophysiology of RTT.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, CA 94305-5323, USA.
authors.forename: Charandle
authors.initials: C
authors.lastname: Jordan
authors.forename: Uta
authors.initials: U
authors.lastname: Francke
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D012333:RNA, Messenger; C502429:Ube3a protein, mouse; D044767:Ubiquitin-Protein Ligases