Abstract
Zfhx2 (also known as zfh-5) encodes a transcription factor containing three homeobox domains and 18 Zn-finger motifs. We have reported that Zfhx2 mRNA is expressed mainly in differentiating neurons in the mouse brain and its expression level is negatively regulated by the antisense transcripts of Zfhx2. Although the expression profile of Zfhx2 suggests that ZFHX2 might have a role in a particular step of neuronal differentiation, the specific function of the gene has not been determined. We generated a Zfhx2-deficient mouse line and performed a comprehensive battery of behavioral tests to elucidate the function of ZFHX2. Homozygous Zfhx2-deficient mice showed several behavioral abnormalities, namely, hyperactivity, enhanced depression-like behaviors, and an aberrantly altered anxiety-like phenotype. These behavioral phenotypes suggest that ZFHX2 might play roles in controlling emotional aspects through the function of monoaminergic neurons where ZFHX2 is expressed. Moreover, considering their phenotypes, the Zfhx2-deficient mice may provide a novel model of human psychiatric disorders.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anxiety / genetics*
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Anxiety / metabolism
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Behavior, Animal / physiology*
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Brain / metabolism
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Depression / genetics*
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Depression / metabolism
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / metabolism
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Hyperkinesis / genetics*
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Hyperkinesis / metabolism
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Mice
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Mice, Knockout
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism
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Neurons / metabolism
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Phenotype
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Transcription Factors / genetics*
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Transcription Factors / metabolism
Substances
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Homeodomain Proteins
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Nerve Tissue Proteins
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RNA, Messenger
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Transcription Factors
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ZFH-5 protein, mouse
Grants and funding
This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas (Molecular Brain Science) (170245 to TY and YK), a Grant-in-Aid for Scientific Research on Innovative Areas (Neocortical Organization) (22123009 to TY), a Grant-in-Aid for Exploratory Research and Integrative Brain Research (IBR-shien), and a Grant-in-Aid for Scientific Research on Innovative Areas (Comprehensive Brain Science Network) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.