Functional analysis of Alivin1/Amigo2

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Alivin1/Amigo2 is a neuronal activity-dependent gene that is a potential therapeutic target for neurodegenerative diseases. This gene was originally discovered by us (1) and has been shown to be involved in neuronal activity-dependent suppression of apoptosis, cell adhesion, migration, and carcinogenesis. Alivin1 encodes a transmembrane protein that has 6.5 times leucine-rich repeats (LRR) and one immunoglobulin (IG) domain. The encoded protein is assumed to interact with its binding partner (s) through these LRR and IG domains and involve in the signal transduction (s) for survival. In order to study biological functions of alivin 1 in mice, we generated the knockout mouse line. Open-field tests were carried out twice with a week interval using the same subjects of alivin1(-/-) and wild type mice (WT). The primary open-field tests showed that the per cent time spent in the central area of the field of alivin1 (-/-) mice was larger than that of WT, suggesting that alivin 1 (-/-) mice have reduced fear and anxiety compared to WT. The comparison between the results of the primary and the secondary tests showed that the locomotor activity of alivin1 (-/-) mice under the familiar environment was larger than that of WT. Alivin1 (-/-) mice kept in their home cages also showed higher locomotor activity than WT. These results suggest that deficiency in alivin1 is associated with enhanced locomotor activity and reduced fear and anxiety.(1) Ono et al.J.Neurosci.23, 5887-5896, 2003.