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¹ INSERM, U433, Institut Fédératif des Neurosciences; Université Claude Bernard Lyon 1; Hospices Civils de Lyon, Lyon, F-69372 France
² Biomolecular Science Center, University of Central Florida, Biomolecular Science, Orlando, Florida 32816-2364, USA
³ Department of Molecular Pharmacology and Neurobiology, Yokohama City University, Graduate School of Medicine, Yokohama 236-0004, Japan
⁴ CREST, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan
⁵ CNRS UMR 5167, Université Claude Bernard Lyon I, Lyon, F-69372 France

Collapsin response mediator proteins (CRMPs) consist of five homologous cytosolic proteins that participate in signal transduction involved in a variety of physiological events. CRMP1 is highly expressed during brain development; however, its functions remains unclear. To gain insight into its function, we generated CRMP1^–/– mice with a knock-in LacZ gene. No gross anatomical changes or behavioral alterations were observed. Expression of CRMP1 was examined by the expression of the knocked-in LacZ gene, in situ hybridization with riboprobes and by imunohistochemistry. CRMP1 was found to be highly expressed in the developing the cerebellum, olfactory bulbs, hypothalamus and retina. In adults, expression level was high in the olfactory bulbs and hippocampus but very low in the retina and cerebellum and undetectable in hypothalamus. To study potential roles of CRMP1, we focused on cerebellum development. CRMP1^–/– mice showed a decrease in the number of granule cells migrating out of explants of developing cerebellum, as did treatment of the explants from normal mice with anti-CRMP1 specific antibodies. CRMP1^–/– mice showed a decrease in granule cell proliferation and apoptosis in external granule cell layers in vivo. Adult cerebellum of CRMP1^–/– did not show any abnormalities.

^aThese authors contributed equally to this work

^* Correspondence: E-mail: thomasse{at}lyon.inserm.fr or pk{at}mail.ucf.edu

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