title: Deletion of JMJD2B in neurons leads to defective spine maturation, hyperactive behavior and memory deficits in mouse.
abstract: JMJD2B is a histone demethylase enzyme that regulates gene expression through demethylation of H3K9me3. Although mutations of JMJD2B have been suggested to be responsible for neurodevelopmental disorders, the function of JMJD2B in the central nervous system (CNS) remains to be elucidated. Here we show that JMJD2B has a critical role in the development of the CNS. We observed JMJD2B expression, which was especially strong in the hippocampus, throughout the CNS from embryonic periods through adulthood. We generated neuron-specific JMJD2B-deficient mice using the cre-loxP system. We found an increase in total spine number, but a decrease in mature spines, in the CA1 region of the hippocampus. JMJD2B-deficient mice exhibited hyperactive behavior, sustained hyperactivity in a novel environment, deficits in working memory and spontaneous epileptic-like seizures. Together these observations indicate that JMJD2B mutant mice display symptoms reminiscent of neurodevelopmental disorders. Our findings provide evidence for the involvement of histone demethylation in the formation of functional neural networks during development.
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Japan.|Japan Science and Technology Agency, CREST, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Japan.|Japan Science and Technology Agency, CREST, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kasai
authors.affiliation: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Onaka
authors.affiliation: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.|iPS Cell-based Research Project on Brain Neuropharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.|Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Suita, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hashimoto
authors.affiliation: Department of Biochemistry, Kinki University Faculty of Medicine, Sayama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Okada
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Japan.|Japan Science and Technology Agency, CREST, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D056547:CA1 Region, Hippocampal / Q000473:pathology*; D049229:Dendritic Spines / Q000473:pathology*; D006948:Hyperkinesis / Q000235:genetics*; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics*; D008568:Memory; D008569:Memory Disorders / Q000235:genetics*; D008570:Memory, Short-Term; D051379:Mice; D018345:Mice, Knockout; D065886:Neurodevelopmental Disorders / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D012640:Seizures / Q000235:genetics*
chemical_list: D056484:Jumonji Domain-Containing Histone Demethylases; C511781:Kdm4b protein, mouse