title: Neuroanatomical and behavioral deficits in mice haploinsufficient for Pericentriolar material 1 (Pcm1).
abstract: The pericentriolar material (PCM) is composed of proteins responsible for microtubule nucleation/anchoring at the centrosome, some of which have been associated with genetic susceptibility to schizophrenia. Here, we show that mice haploinsufficient for Pericentriolar material 1 (Pcm1(+/-)), which encodes a component of the PCM found to bear rare loss of function mutations in patients with psychiatric illness, manifest neuroanatomical phenotypes and behavioral abnormalities. Using ex vivo magnetic resonance imaging of the Pcm1(+/-) brain, we detect reduced whole brain volume. Pcm1 mutant mice show impairment in social interaction, specifically in the social novelty phase, but not in the sociability phase of the three-chamber social interaction test. In contrast, Pcm1(+/-) mice show normal preference for a novel object, suggesting specific impairment in response to novel social stimulus. In addition, Pcm1(+/-) mice display significantly reduced rearing activity in the open field. Pcm1(+/-) mice behave normally in the elevated plus maze, rotarod, prepulse inhibition, and progressive ratio tests. Together, our results suggest that haploinsufficiency at the Pcm1 locus can induce a range of neuroanatomical and behavioral phenotypes that support the candidacy of this locus in neuropsychiatric disorders.
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, United States.
authors.forename: Sandra
authors.initials: S
authors.lastname: Zoubovsky
authors.affiliation: Center for Human Disease Modeling, Duke University Medical Center, Durham, NC 27710, United States.
authors.forename: Edwin C
authors.initials: EC
authors.lastname: Oh
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, United States.
authors.forename: Tyler
authors.initials: T
authors.lastname: Cash-Padgett
authors.affiliation: Department of Psychological and Brain Sciences, Johns Hopkins University School of Arts and Sciences, 3400 N. Charles St., Baltimore, MD 21218, United States.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Johnson
authors.affiliation: Department of Radiology, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, United States.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Hou
authors.affiliation: Department of Radiology, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, United States.
authors.forename: Susumu
authors.initials: S
authors.lastname: Mori
authors.affiliation: Department of Psychological and Brain Sciences, Johns Hopkins University School of Arts and Sciences, 3400 N. Charles St., Baltimore, MD 21218, United States.
authors.forename: Michela
authors.initials: M
authors.lastname: Gallagher
authors.affiliation: Center for Human Disease Modeling, Duke University Medical Center, Durham, NC 27710, United States.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Katsanis
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, United States.
authors.forename: Akira
authors.initials: A
authors.lastname: Sawa
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, United States. Electronic address: hjaarop@jhmi.edu.
authors.forename: Hanna
authors.initials: H
authors.lastname: Jaaro-Peled
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000235:genetics*; D005106:Exploratory Behavior; D057895:Haploinsufficiency; D008297:Male; D001523:Mental Disorders / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D008817:Mice, Mutant Strains; D009043:Motor Activity; D009929:Organ Size; D065808:Prepulse Inhibition; D013216:Reflex, Startle; D012559:Schizophrenia / Q000235:genetics; D012919:Social Behavior
chemical_list: D018797:Cell Cycle Proteins; C490114:Pcm1 protein, mouse
keywords: Behavior; Mouse model; Neuroanatomy; Pcm1; Schizophrenia