Disc1 is mutated in the 129S6/SvEv strain and modulates working memory in mice
- Hiroko Koike*,†,‡,
- P. Alexander Arguello§,‡,
- Mirna Kvajo*,†,
- Maria Karayiorgou*,¶, and
- Joseph A. Gogos†,§,¶
- *Human Neurogenetics Laboratory, The Rockefeller University, 1230 York Avenue, New York, NY 10021;
- †Department of Physiology and Cellular Biophysics, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032; and
- §Center for Neurobiology and Behavior, Columbia University Medical Center, 701 West 168th Street, New York, NY 10032
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Communicated by David E. Housman, Massachusetts Institute of Technology, Cambridge, MA, December 26, 2005
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↵ ‡H.K. and P.A.A. contributed equally to this work. (received for review December 15, 2005)
Abstract
Disrupted-In-Schizophrenia (DISC1) is a leading candidate schizophrenia susceptibility gene. Here, we describe a deletion variant in mDisc1 specific to the 129S6/SvEv strain that introduces a termination codon at exon 7, abolishes production of the full-length protein, and impairs working memory performance when transferred to the C57BL/6J genetic background. Our findings provide insights into how DISC1 variation contributes to schizophrenia susceptibility in humans and the behavioral divergence between 129S6/SvEv and C57BL/6J mouse strains and have implications for modeling psychiatric diseases in mice.
Footnotes
- ¶To whom correspondence may be addressed. E-mail: karayim{at}rockefeller.edu or jag90{at}columbia.edu
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Author contributions: H.K., P.A.A., M. Karayiorgou, and J.A.G. designed research; H.K., P.A.A., and M. Kvajo performed research; H.K., P.A.A., M. Kvajo, M. Karayiorgou, and J.A.G. analyzed data; and H.K., P.A.A., M. Kvajo, M. Karayiorgou, and J.A.G. wrote the paper.
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Conflict of interest statement: No conflicts declared.
- © 2006 by The National Academy of Sciences of the USA
