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https://doi.org/10.1371/journal.pone.0014185
Title: | Phenotypic characterization of transgenic mice overexpressing neuregulin-1 | Authors: | Kato T. Kasai A. Mizuno M. Fengyi L. Shintani N. Maeda S. Yokoyama M. Ozaki M. Nawa H. |
Keywords: | 2',3' cyclic nucleotide 3' phosphodiesterase complementary DNA dopamine elongation factor 1alpha green fluorescent protein myelin basic protein neu differentiation factor parvalbumin tyrosine 3 monooxygenase complementary DNA dopamine neu differentiation factor animal behavior animal experiment animal tissue article cognition controlled study dopamine brain level fear frontal cortex GABAergic system gene overexpression hippocampus knockout mouse locomotion male mouse myelination neurochemistry nonhuman phenotypic variation prepulse inhibition schizophrenia scoring system signal transduction social interaction social isolation transgenic mouse alternative RNA splicing animal cytology frontal lobe gene expression regulation genetic predisposition genetics glia heterozygote metabolism mutation pathology phenotype promoter region Mus Mus musculus Alternative Splicing Animals DNA, Complementary Dopamine Frontal Lobe Gene Expression Regulation Genetic Predisposition to Disease Heterozygote Mice Mice, Transgenic Mutation Neuregulin-1 Neuroglia Phenotype Promoter Regions, Genetic |
Issue Date: | 2010 | Citation: | Kato T., Kasai A., Mizuno M., Fengyi L., Shintani N., Maeda S., Yokoyama M., Ozaki M., Nawa H. (2010). Phenotypic characterization of transgenic mice overexpressing neuregulin-1. PLoS ONE 5 (12) : e14185. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0014185 | Rights: | Attribution 4.0 International | Abstract: | Background: Neuregulin-1 (NRG1) is one of the susceptibility genes for schizophrenia and implicated in the neurotrophic regulation of GABAergic and dopaminergic neurons, myelination, and NMDA receptor function. Postmortem studies often indicate a pathologic association of increased NRG1 expression or signaling with this illness. However, the psychobehavioral implication of NRG1 signaling has mainly been investigated using hypomorphic mutant mice for individual NRG1 splice variants. Methodology/Principal Findings: To assess the behavioral impact of hyper NRG1 signaling, we generated and analyzed two independent mouse transgenic (Tg) lines carrying the transgene of green fluorescent protein (GFP)-tagged type-1 NRG1 cDNA. The promoter of elongation-factor 1? gene drove ubiquitous expression of GFP-tagged NRG1 in the whole brain. As compared to control littermates, both heterozygous NRG1-Tg lines showed increased locomotor activity, a nonsignificant trend toward decreasing prepulse inhibition, and decreased context-dependent fear learning but exhibited normal levels of tone-dependent learning. In addition, social interaction scores in both Tg lines were reduced in an isolationinduced resident-intruder test. There were also phenotypic increases in a GABAergic marker (parvalbumin) as well as in myelination markers (myelin basic protein and 2?,3?-cyclic nucleotide 3?-phosphodiesterase) in their frontal cortex, indicating the authenticity of NRG1 hyper-signaling, although there were marked decreases in tyrosine hydroxylase levels and dopamine content in the hippocampus. Conclusions: These findings suggest that aberrant hyper-signals of NRG1 also disrupt various cognitive and behavioral processes. Thus, neuropathological implication of hyper NRG1 signaling in psychiatric diseases should be evaluated with further experimentation. © 2010 Kato et al. | Source Title: | PLoS ONE | URI: | https://scholarbank.nus.edu.sg/handle/10635/161796 | ISSN: | 19326203 | DOI: | 10.1371/journal.pone.0014185 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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