Neuregulin 3 Knockout Mice Exhibit Behaviors Consistent with Psychotic Disorders.
Neuregulin 3 (NRG3) is a paralog of NRG1. Genetic studies in schizophrenia demonstrate that risk variants in NRG3 are associated with cognitive and psychotic symptom severity, and several intronic single nucleotide polymorphisms in NRG3 are associated with delusions in patients with schizophrenia. In order to gain insights into the biological function of the gene, we generated a novel Nrg3 knockout (KO) mouse model and tested for neurobehavioral phenotypes relevant to psychotic disorders. KO mice displayed novelty-induced hyperactivity, impaired prepulse inhibition of the acoustic startle response, and deficient fear conditioning. No gross cytoarchitectonic or layer abnormalities were noted in the brain of KO mice. Our findings suggest that deletion of the Nrg3 gene leads to alterations consistent with aspects of schizophrenia. We propose that KO mice will provide a valuable animal model to determine the role of the NRG3 in the molecular pathogenesis of schizophrenia and other psychotic disorders.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Md., USA.
Lindsay N
LN
Hayes
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Md., USA.
Alexey
A
Shevelkin
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md., USA; Predoctoral Training Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, Md., USA.
Mariela
M
Zeledon
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md., USA.
Gary
G
Steel
Department of Medical Genetics, National Taiwan University Hospital, Taipei City, Taiwan, ROC.
Pei-Lung
PL
Chen
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md., USA.
Cassandra
C
Obie
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md., USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Md., USA.
Ann
A
Pulver
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md., USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Md., USA.
Dimitrios
D
Avramopoulos
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md., USA.
David
D
Valle
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md., USA; Predoctoral Training Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, Md., USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Md., USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Md., USA.
Akira
A
Sawa
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Md., USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Md., USA.
Mikhail V
MV
Pletnikov
Fear conditioning; Hyperactivity; Neuregulin 3; Prepulse inhibition; Psychotic disorders