title: Abnormal behaviors and developmental disorder of hippocampus in zinc finger protein 521 (ZFP521) mutant mice.
abstract: Zinc finger protein 521 (ZFP521) regulates a number of cellular processes in a wide range of tissues, such as osteoblast formation and adipose commitment and differentiation. In the field of neurobiology, it is reported to be an essential factor for transition of epiblast stem cells into neural progenitors in vitro. However, the role of ZFP521 in the brain in vivo still remains elusive. To elucidate the role of ZFP521 in the mouse brain, we generated mice lacking exon 4 of the ZFP521 gene. The birth ratio of our ZFP521Δ/Δ mice was consistent with Mendel's laws. Although ZFP521Δ/Δ pups had no apparent defect in the body and were indistinguishable from ZFP521+/+ and ZFP521+/Δ littermates at the time of birth, ZFP521Δ/Δ mice displayed significant weight reduction as they grew, and most of them died before 10 weeks of age. They displayed abnormal behavior, such as hyper-locomotion, lower anxiety and impaired learning, which correspond to the symptoms of schizophrenia. The border of the granular cell layer of the dentate gyrus in the hippocampus of the mice was indistinct and granular neurons were reduced in number. Furthermore, Sox1-positive neural progenitor cells in the dentate gyrus and cerebellum were significantly reduced in number. Taken together, these findings indicate that ZFP521 directly or indirectly affects the formation of the neuronal cell layers of the dentate gyrus in the hippocampus, and thus ZFP521Δ/Δ mice displayed schizophrenia-relevant symptoms. ZFP521Δ/Δ mice may be a useful research tool as an animal model of schizophrenia.
authors.affiliation: Department of Circulatory Physiology, Ehime University, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Ohkubo
authors.affiliation: Department of Hematology, Clinical Immunology and Infectious Diseases, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Matsubara
authors.affiliation: Department of Hematology, Clinical Immunology and Infectious Diseases, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Yamanouchi
authors.affiliation: Department of Circulatory Physiology, Ehime University, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Akazawa
authors.affiliation: Department of Circulatory Physiology, Ehime University, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Aoto
authors.affiliation: Department of Circulatory Physiology, Ehime University, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Pathophysiology, College of Pharmaceutical Sciences, School of Clinical Pharmacy, Matsuyama University, Matsuyama, Ehime, Japan.
authors.forename: Ikuya
authors.initials: I
authors.lastname: Sakai
authors.affiliation: Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe, Hyogo, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Abe
authors.affiliation: Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe, Hyogo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.affiliation: Department of Anatomy and Embryology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Matsuda
authors.affiliation: Department of Hematology, Clinical Immunology and Infectious Diseases, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Yasukawa
authors.affiliation: Department of Circulatory Physiology, Ehime University, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Mitsuda
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D018891:Dentate Gyrus / Q000378:metabolism; D004195:Disease Models, Animal; D005091:Exons; D005260:Female; D023061:Gene Order; D018390:Gene Targeting; D056726:Genetic Association Studies; D056426:Genetic Loci; D005838:Genotype; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008607:Intellectual Disability / Q000235:genetics*; D008017:Life Expectancy; D008297:Male; D051379:Mice; D009154:Mutation; D058953:Neural Stem Cells / Q000166:cytology; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C472572:Evi3 protein, mouse; D014157:Transcription Factors