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Molecular and Cellular Biology, August 2005, p. 7278-7288, Vol. 25, No. 16
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.16.7278-7288.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Neurexophilin 3 Is Highly Localized in Cortical and Cerebellar Regions and Is Functionally Important for Sensorimotor Gating and Motor Coordination

Vassilios Beglopoulos,^1, Monique Montag-Sallaz,² Astrid Rohlmann,¹ Kerstin Piechotta,¹ Mohiuddin Ahmad,¹ Dirk Montag,² and Markus Missler^1,3*

Center for Physiology and Pathophysiology, Georg-August University, Göttingen, Germany,¹ Neurogenetics Research Group, Leibniz Institute for Neurobiology, Magdeburg, Germany,² Department of Genetics and Molecular Neurobiology, Institute of Biology, Otto-von-Guericke-University, Magdeburg, Germany³

Received 11 March 2005/ Returned for modification 26 April 2005/ Accepted 1 June 2005

Neurexophilin 3 (Nxph3) is a specific ligand of synaptic -neurexins that are essential for efficient neurotransmitter release. Previous biochemical work demonstrated that Nxph3 interacts with an extracellular domain of -neurexins in a tight complex; however, no information is available on the localization or functional role of Nxph3 in the brain. Here, we generated lacZ reporter gene knock-in mice to investigate the distribution of Nxph3 at the single-cell level and Nxph3 knockout mice to examine its functional importance. Nxph3 expression was restricted mostly to subplate-derived neurons in cortical layer 6b, granule cells in the vestibulocerebellum, and Cajal-Retzius cells during development. Colabeling experiments demonstrated that neurons expressing Nxph3 do not belong to a uniform cell type. Morphological analyses and systematic behavioral testing of knockout mice revealed no anatomical defects but uncovered remarkable functional abnormalities in sensory information processing and motor coordination, evident by increased startle response, reduced prepulse inhibition, and poor rotarod performance. Since Nxph3-deficient mice behaved normally while performing a number of other tasks, our data suggest an important role for Nxph3 as a locally and temporally regulated neuropeptide-like molecule, presumably acting in a complex with -neurexins in select neuronal circuits.

Present address: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.

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