title: The loss of methyl-CpG binding protein 1 leads to autism-like behavioral deficits.
abstract: Methyl-CpG binding proteins (MBDs) are central components of DNA methylation-mediated epigenetic gene regulation. Alterations of epigenetic pathways are known to be associated with several neurodevelopmental disorders, particularly autism. Our previous studies showed that the loss of Mbd1 led to reduced hippocampal neurogenesis and impaired learning in mice. However, whether MBD1 regulates the autism-related cognitive functions remains unknown. Here we show that Mbd1 mutant (Mbd1(-/-)) mice exhibit several core deficits frequently associated with autism, including reduced social interaction, learning deficits, anxiety, defective sensory motor gating, depression and abnormal brain serotonin activity. Furthermore, we find that Mbd1 can directly regulate the expression of Htr2c, one of the serotonin receptors, by binding to its promoter, and the loss of Mbd1 led to elevated expression of Htr2c. Our results, therefore, demonstrate the importance of epigenetic regulation in mammalian brain development and cognitive functions. Understanding how the loss of Mbd1 could lead to autism-like behavioral phenotypes would reveal much-needed information about the molecular pathogenesis of autism.
authors.affiliation: Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Allan
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Liang
authors.forename: Yuping
authors.initials: Y
authors.lastname: Luo
authors.forename: Changhui
authors.initials: C
authors.lastname: Pak
authors.forename: Xuekun
authors.initials: X
authors.lastname: Li
authors.forename: Keith E
authors.initials: KE
authors.lastname: Szulwach
authors.forename: Dahua
authors.initials: D
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000819:Animal Communication; D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001321:Autistic Disorder / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D003863:Depression / Q000503:physiopathology; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C489323:Mbd1 protein, mouse; D011985:Receptors, Serotonin