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Molecular and Cellular Biology, May 2005, p. 4166-4175, Vol. 25, No. 10
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.10.4166-4175.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Neuronal Leucine-Rich Repeat Protein 4 Functions in Hippocampus-Dependent Long-Lasting Memory

Laboratory of Cell Growth and Differentiation,¹ Laboratory of Neuclear Signaling, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan,² Division of Neuronal Network, Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan,³ Department of Anatomy and Neurobiology, Wakayama Medical University, 811-1 Kimidera, Wakayama 641-8509, Japan⁴

Received 11 November 2004/ Accepted 13 February 2005

Neuronal leucine-rich repeat proteins (NLRRs) are type I transmembrane proteins and expressed in neuronal tissues, but their function remains unknown. Here, we describe the identification and characterization of a new member of the NLRR family, NLRR4, and its potential role in long-lasting memory. We generated NLRR4-deficient (NLRR4^–/–) mice and found that they showed impaired memory retention. In hippocampus-dependent learning tasks, NLRR4^–/– mice were able to learn and maintain the memories for one day but unable to retain the memories for four days after learning. In contrast, in a hippocampus-independent task, NLRR4^–/– mice were able to retain the memory normally for at least seven days. These results suggest that NLRR4 plays a key role in hippocampus-dependent long-lasting memory.

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