QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 22, 2008, 28(43):10893-10904; doi:10.1523/JNEUROSCI.3299-08.2008

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Shen, S. Articles by St Clair, D. Search for Related Content PubMed PubMed Citation Articles by Shen, S. Articles by St Clair, D.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Schizophrenia-Related Neural and Behavioral Phenotypes in Transgenic Mice Expressing Truncated Disc1

Sanbing Shen,^1 * Bing Lang,^1 * Chizu Nakamoto,¹ Feng Zhang,¹ Jin Pu,¹ Soh-Leh Kuan,¹ Christina Chatzi,¹ Shuisheng He,² Iain Mackie,³ Nicholas J. Brandon,⁴ Karen L. Marquis,⁴ Mark Day,⁵ Orest Hurko,^5,6 Colin D. McCaig,¹ Gernot Riedel,¹ and David St Clair¹

¹School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom, ²School of Engineering, University of Aberdeen, Aberdeen AB24 3UE, United Kingdom, ³School of Biological Sciences, University of Aberdeen, Aberdeen AB24 2TZ, United Kingdom, ⁴Neuroscience Discovery, Wyeth Research, Princeton, New Jersey 08543, ⁵Discovery Translational Medicine, Wyeth Research, Collegeville, Pennsylvania 19426, and ⁶Translational Medicine Research Collaboration, University of Dundee, Sir James Black Center 4L6-210, Dundee DD1 5EH, United Kingdom

Correspondence should be addressed to Sanbing Shen, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK. Email: sanbing.shen{at}abdn.ac.uk

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 generated Disc1_tr transgenic mice expressing 2 copies of truncated Disc1 encoding 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. Disc1_tr transgenic 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 in Disc1_tr transgenic mice are consistent with findings in severe schizophrenia.

Key words: bacterial artificial chromosome; behavior; Disc1; neuroanatomy; schizophrenia; transgenic mice

---

Received July 15, 2008; revised Aug. 28, 2008; accepted Sept. 9, 2008.

Correspondence should be addressed to Sanbing Shen, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK. Email: sanbing.shen{at}abdn.ac.uk

This article has been cited by other articles:

				H. Jaaro-Peled, Y. Ayhan, M. V. Pletnikov, and A. Sawa Review of Pathological Hallmarks of Schizophrenia: Comparison of Genetic Models With Patients and Nongenetic Models Schizophr Bull, November 10, 2009; (2009) sbp133v1. [Abstract] [Full Text] [PDF]

				N. J. Brandon, J. K. Millar, C. Korth, H. Sive, K. K. Singh, and A. Sawa Understanding the Role of DISC1 in Psychiatric Disease and during Normal Development J. Neurosci., October 14, 2009; 29(41): 12768 - 12775. [Abstract] [Full Text] [PDF]

				K. Nakata, B. K. Lipska, T. M. Hyde, T. Ye, E. N. Newburn, Y. Morita, R. Vakkalanka, M. Barenboim, Y. Sei, D. R. Weinberger, et al. DISC1 splice variants are upregulated in schizophrenia and associated with risk polymorphisms PNAS, September 15, 2009; 106(37): 15873 - 15878. [Abstract] [Full Text] [PDF]

				J. J. McGrath and L. J. Richards Why Schizophrenia Epidemiology Needs Neurobiology--and Vice Versa Schizophr Bull, May 1, 2009; 35(3): 577 - 581. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help