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Phenotypic characterization of C57BL/6J mice carrying the Disc1 gene from the 129S6/SvEv strain

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Abstract

Disruption of disrupted-in-schizophrenia 1 (DISC1), a candidate susceptibility gene for schizophrenia, was first identified in a large Scottish family in which many members suffered from various psychiatric disorders, including schizophrenia. To model the Scottish DISC1 truncation, we established a Disc1 mutant mouse line in which the 129S6/SvEv 25-bp deletion variant was transferred into the C57BL/6J strain by backcrossing. A battery of behavioral tasks was conducted to evaluate the basic behaviors and cognitive function of these mice. In heterozygote and homozygote Disc1 mutant (Het and Homo) mice, behavioral impairments were noted in working memory test which is thought to be mediated by the function of the medial prefrontal cortex (mPFC). The properties of mPFC neurons were characterized in both morphological and physiological aspects. The dendritic diameters were decreased in layer II/III mPFC pyramidal neurons of Het and Homo mice, whereas a significant reduction in spine density was observed in Homo mice. Neuronal excitability was declined in layer II/III mPFC pyramidal neurons of Het and Homo mice, yet increased transmitter release was identified in Homo mice. Thus, the structural and functional alterations of the mPFC in Het and Homo mice might account for their cognitive impairment. Since most of the gene knockout mice are generated from 129 substrain-derived embryonic stem cells, potential Disc1 deficiency should be considered.

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Acknowledgments

This work was supported by National Science Council of the Republic of China, Grant numbers: NSC 98-2410-H-002-033 (to L.-J. L.), NSC 99-2628-B-002-052-MY3 (to L.-J. L.) and NSC99-2410-H-002-088-MY3 (to W.-S. L.).

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Authors and Affiliations

  1. Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Ren-Ai Rd, Section 1, Taipei, 100, Taiwan, ROC

    Liang-Wen Juan, Chun-Chieh Liao & Li-Jen Lee

  2. Department of Psychology, Taiwan University Hospital, Taipei, Taiwan, ROC

    Wen-Sung Lai, Chia-Yuan Chang & Ju-Chun Pei

  3. Graduate Institute of Brain and Mind Sciences, Taiwan University Hospital, Taipei, Taiwan, ROC

    Wen-Sung Lai, Wan-Rong Wong, Chih-Min Liu, Hai-Gwo Hwu & Li-Jen Lee

  4. Neurobiology and Cognitive Sciences Center, National Taiwan University, Taipei, Taiwan, ROC

    Wen-Sung Lai, Chih-Min Liu, Hai-Gwo Hwu & Li-Jen Lee

  5. Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan, ROC

    Chih-Min Liu & Hai-Gwo Hwu

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  1. Liang-Wen Juan
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  2. Chun-Chieh Liao
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  3. Wen-Sung Lai
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  9. Li-Jen Lee
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Correspondence to Li-Jen Lee.

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L.-W. Juan and C.-C. Liao contributed equally to this work.

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Juan, LW., Liao, CC., Lai, WS. et al. Phenotypic characterization of C57BL/6J mice carrying the Disc1 gene from the 129S6/SvEv strain. Brain Struct Funct 219, 1417–1431 (2014). https://doi.org/10.1007/s00429-013-0577-8

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