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Expression of the G72/G30 gene in transgenic mice induces behavioral changes

Molecular Psychiatry volume 19, pages 175–183 (2014)Cite this article

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Abstract

The G72/G30 gene complex is a candidate gene for schizophrenia and bipolar disorder. However, G72 and G30 mRNAs are expressed at very low levels in human brain, with only rare splicing forms observed. We report here G72/G30 expression profiles and behavioral changes in a G72/G30 transgenic mouse model. A human BAC clone containing the G72/G30 genomic region was used to establish the transgenic mouse model, on which gene expression studies, western blot and behavioral tests were performed. Relative to their minimal expression in humans, G72 and G30 mRNAs were highly expressed in the transgenic mice, and had a more complex splicing pattern. The highest G72 transcript levels were found in testis, followed by cerebral cortex, with very low or undetectable levels in other tissues. No LG72 (the long putative isoform of G72) protein was detected in the transgenic mice. Whole-genome expression profiling identified 361 genes differentially expressed in transgenic mice compared with wild-type, including genes previously implicated in neurological and psychological disorders. Relative to wild-type mice, the transgenic mice exhibited fewer stereotypic movements in the open field test, higher baseline startle responses in the course of the prepulse inhibition test, and lower hedonic responses in the sucrose preference test. The transcriptome profile changes and multiple mouse behavioral effects suggest that the G72 gene may play a role in modulating behaviors relevant to psychiatric disorders.

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Acknowledgements

This work was supported by 1R21MH083521, 4R33MH083521 (to CL) and the Geraldi Norton Foundation and the Eklund Family. We are grateful to Dr Mirna Kvajo and Dr Joseph A Gogos at Columbia University, and Dr Guang Chen and Dr Husseini K Manji at NIMH for anti-G72 antibodies. We thank Dr Cristianne RM Frazier, Dr Jeff A Beeler and Dr Xiaoxi Zhuang at The University of Chicago for technical assistance and data analysis of the mouse sucrose preference test.

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Authors and Affiliations

  1. Department of Psychiatry, Institute of Human Genetics, The University of Illinois at Chicago, Chicago, IL, USA

    L Cheng, C Zhang & C Liu

  2. Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama 351-0198, and Sangenjaya Station Mental Health Clinic, Tokyo, Japan

    E Hattori

  3. Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan

    A Nakajima

  4. Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA

    N S Woehrle, M D Opal, K Grennan, S C Dulawa & E S Gershon

  5. Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center, New Orleans, LA, USA

    Y-P Tang

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Correspondence to C Liu.

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The authors declared no biomedical financial interests or conflict of interest. The views expressed in this manuscript are not necessarily those of NIH. The sequences of 13 novel G72 splicing forms identified in human and transgenic mouse model have been accepted by NCBI GenBank (www.ncbi.nlm.nih.gov/genbank), with accession numbers as indicated in Figure 1b.

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Cheng, L., Hattori, E., Nakajima, A. et al. Expression of the G72/G30 gene in transgenic mice induces behavioral changes. Mol Psychiatry 19, 175–183 (2014). https://doi.org/10.1038/mp.2012.185

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