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Human Molecular Genetics Advance Access published online on September 28, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl402
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© 2006 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received July 6, 2006
Revised September 18, 2006
Accepted September 18, 2006

Article

Secretin receptor deficient mice exhibit impaired synaptic plasticity and social behavior

Ichiko Nishijima 1 *, Takanori Yamagata 2, Corinne M. Spencer 3, Edwin J. Weeber 4, Olga Alekseyenko 3, J. David Sweatt 5, Mariko Y Momoi 6, Masayuki Ito 7, Dawna L. Armstrong 8, David L. Nelson 3, Richard Paylor 9, and Allan Bradley 10

1 Center for Molecular and Human Genetics, Columbus Children's Research Institute, The Ohio State University, Columbus, OH 43205, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
2 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Jichi Medical School, Tochigi 329-0498, Japan
3 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
4 Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA
5 Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
6 Department of Pediatrics, Jichi Medical School, Tochigi 329-0498, Japan
7 National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan
8 Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA
9 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
10 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; The Wellcome Trust Sanger Institute, Cambridge, UK

* To whom correspondence should be addressed.
Ichiko Nishijima, E-mail: nishijii{at}pediatrics.ohio-state.edu


  Abstract

Secretin is a peptide hormone released from the duodenum to stimulate secretion of digestive juice by the pancreas. Secretin also functions as a neuropeptide hormone in the brain and exogenous administration has been reported to alleviate symptoms in some patients with autism. We have generated secretin receptor deficient mice to explore the relationship between secretin signaling in the brain and behavioral phenotypes. Secretin receptor deficient mice are overtly normal and fertile; however, synaptic plasticity in the hippocampus is impaired and there are slightly fewer dendritic spines in the CA1 hippocampal pyramidal cells. Furthermore, secretin receptor deficient mice show abnormal social and cognitive behaviors. These findings suggest that the secretin receptor system has an important role in the central nervous system relating to social behavior.


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