Original Research Article

Molecular Psychiatry (2004) 9, 1100–1110. doi:10.1038/sj.mp.4001574 Published online 21 September 2004

Expression of disrupted in schizophrenia 1 (DISC1) protein in the adult and developing mouse brain indicates its role in neurodevelopment

I L Schurov1, E J Handford1, N J Brandon1 and P J Whiting1

1Merck Sharp & Dohme, The Neuroscience Research Centre, Terlings Park, Harlow, Essex, UK

Correspondence: I Schurov, Merck Sharp and Dohme, The Neuroscience Research Centre, Terlings Park, Harlow, Essex, CM20 2QR, UK. E-mail: irina_schurov@merck.com

Received 17 February 2004; Revised 13 July 2004; Accepted 23 July 2004; Published online 21 September 2004.

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Abstract

Disrupted in Schizophrenia 1 (DISC1) was identified as a potential susceptibility gene for schizophrenia due to its disruption by a balanced t(1;11) (q42;q14) translocation, which has been shown to cosegregate with major psychiatric disease in a large Scottish family. We have recently presented evidence that DISC1 exists in a neurodevelopmentally regulated protein complex with Nudel. In this study, we report the protein expression profile of DISC1 in the adult and developing mouse brain utilizing immunohistochemistry and quantitative Western blot. In the adult mouse brain, DISC1 is expressed in neurons within various brain areas including the olfactory bulb, cortex, hippocampus, hypothalamus, cerebellum and brain stem. During development, DISC1 protein is detected at all stages, from E10 to 6 months old, with two significant peaks of protein expression of a DISC1 isoform at E13.5 and P35. Interestingly, these time points correspond to critical stages during mouse development, the active neurogenesis period in the developing brain and the period of puberty. Together, these results suggest that DISC1 may play a critical role in brain development, consistent with the neurodevelopmental hypothesis of the etiology of schizophrenia.

Keywords:

schizophrenia, DISC1, development, brain

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