Schizophrenia-Related Neural and Behavioral Phenotypes in Transgenic Mice Expressing Truncated Disc1
| Autor: | Christina Chatzi, Karen L. Marquis, Soh Leh Kuan, Nicholas J. Brandon, Gernot Riedel, David St Clair, Shuisheng He, Orest Hurko, Bing Lang, Feng Zhang, Jin Pu, Chizu Nakamoto, Iain Mackie, Sanbing Shen, Colin D. McCaig, Mark Day |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Positional cloning
Transgene Green Fluorescent Proteins Hippocampus Mice Transgenic Nerve Tissue Proteins Corpus callosum DISC1 Mice medicine Neurites Animals Prefrontal cortex Cells Cultured Swimming Cerebral Cortex Neurons Analysis of Variance biology Behavior Animal General Neuroscience Age Factors Articles Embryo Mammalian Mice Inbred C57BL Disease Models Animal Inhibition Psychological medicine.anatomical_structure Parvalbumins Phenotype Animals Newborn Bromodeoxyuridine Gene Expression Regulation Hindlimb Suspension Cerebral cortex Mutation biology.protein Schizophrenia Neuroscience Parvalbumin |
| Popis: | Disrupted-in-Schizophrenia-1(DISC1), identified by positional cloning of a balanced translocation (1;11) with the breakpoint in intron 8 of a large Scottish pedigree, is associated with a range of neuropsychiatric disorders including schizophrenia. To model this mutation in mice, we have generatedDisc1trtransgenic mice expressing 2 copies of truncatedDisc1encoding the first 8 exons using a bacterial artificial chromosome (BAC). With this partial simulation of the human situation, we have discovered a range of phenotypes including a series of novel features not previously reported.Disc1trtransgenic mice display enlarged lateral ventricles, reduced cerebral cortex, partial agenesis of the corpus callosum, and thinning of layers II/III with reduced neural proliferation at midneurogenesis. Parvalbumin GABAergic neurons are reduced in the hippocampus and medial prefrontal cortex, and displaced in the dorsolateral frontal cortex. In culture, transgenic neurons grow fewer and shorter neurites. Behaviorally, transgenic mice exhibit increased immobility and reduced vocalization in depression-related tests, and impairment in conditioning of latent inhibition. These abnormalities inDisc1trtransgenic mice are consistent with findings in severe schizophrenia. |
| Databáze: | OpenAIRE |
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