Abstract
The neuronal PAS domain protein 3 (NPAS3) gene encoding a brain-enriched transcription factor was recently found to be disrupted in a family suffering from schizophrenia. Mice harboring compound disruptions in the NPAS3 and related NPAS1 genes manifest behavioral and neuroanatomical abnormalities reminiscent of schizophrenia. Herein we demonstrate that Npas3-/- mice are deficient in expression of hippocampal FGF receptor subtype 1 mRNA, most notably in the dentate gyrus. In vivo BrdUrd-labeling shows that basal neural precursor cell proliferation in the dentate gyrus of Npas3-/- mice is reduced by 84% relative to wild-type littermates. We propose that a deficiency in adult neurogenesis may cause the behavioral and neuroanatomical abnormalities seen in Npas3-/- mice, and we speculate that impaired neurogenesis may be involved in the pathophysiology of schizophrenia.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism*
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Behavior, Animal
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Cell Proliferation
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Dentate Gyrus / anatomy & histology
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Dentate Gyrus / chemistry
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Dentate Gyrus / cytology
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Dentate Gyrus / growth & development
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Female
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Fibroblast Growth Factor 2 / pharmacology
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Hippocampus / chemistry
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Hippocampus / cytology*
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Male
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Mice
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Mice, Neurologic Mutants
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Neurons / cytology*
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Neurons / metabolism
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Neurons / physiology
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Oligonucleotide Array Sequence Analysis
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RNA, Messenger / metabolism
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Schizophrenia / genetics*
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Schizophrenia / metabolism
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Stem Cells / metabolism
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Npas3 protein, mouse
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RNA, Messenger
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Fibroblast Growth Factor 2