title: Targeted deletion of the C-terminus of the mouse adenomatous polyposis coli tumor suppressor results in neurologic phenotypes related to schizophrenia.
abstract: BACKGROUND
  Loss of adenomatous polyposis coli (APC) gene function results in constitutive activation of the canonical Wnt pathway and represents the main initiating and rate-limiting event in colorectal tumorigenesis. APC is likely to participate in a wide spectrum of biological functions via its different functional domains and is abundantly expressed in the brain as well as in peripheral tissues. However, the neuronal function of APC is poorly understood. To investigate the functional role of Apc in the central nervous system, we analyzed the neurological phenotypes of Apc1638T/1638T mice, which carry a targeted deletion of the 3' terminal third of Apc that does not affect Wnt signaling.
  
  
  RESULTS
  A series of behavioral tests revealed a working memory deficit, increased locomotor activity, reduced anxiety-related behavior, and mildly decreased social interaction in Apc1638T/1638T mice. Apc1638T/1638T mice showed abnormal morphology of the dendritic spines and impaired long-term potentiation of synaptic transmission in the hippocampal CA1 region. Moreover, Apc1638T/1638T mice showed abnormal dopamine and serotonin distribution in the brain. Some of these behavioral and neuronal phenotypes are related to symptoms and endophenotypes of schizophrenia.
  
  
  CONCLUSIONS
  Our results demonstrate that the C-terminus of the Apc tumor suppressor plays a critical role in cognitive and neuropsychiatric functioning. This finding suggests a potential functional link between the C-terminus of APC and pathologies of the central nervous system.
authors.forename: Takanori
authors.initials: T
authors.lastname: Onouchi
authors.affiliation: Department of Anatomy I, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan. kkatsu-tky@umin.ac.jp.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Sakai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimomura
authors.forename: Ron
authors.initials: R
authors.lastname: Smits
authors.forename: Chiho
authors.initials: C
authors.lastname: Sumi-Ichinose
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kurosumi
authors.forename: Keizo
authors.initials: K
authors.lastname: Takao
authors.forename: Ryuji
authors.initials: R
authors.lastname: Nomura
authors.forename: Akiko
authors.initials: A
authors.lastname: Iizuka-Kogo
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
authors.forename: Kazunao
authors.initials: K
authors.lastname: Kondo
authors.forename: Tetsu
authors.initials: T
authors.lastname: Akiyama
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyakawa
authors.forename: Riccardo
authors.initials: R
authors.lastname: Fodde
authors.forename: Takao
authors.initials: T
authors.lastname: Senda
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D003863:Depression / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D005106:Exploratory Behavior; D018390:Gene Targeting; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009043:Motor Activity; D010641:Phenotype; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D017384:Sequence Deletion; D012701:Serotonin / Q000378:metabolism; D012919:Social Behavior; D013329:Structure-Activity Relationship; D013569:Synapses / Q000473:pathology / Q000648:ultrastructure; D009435:Synaptic Transmission
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D012701:Serotonin; D004298:Dopamine