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The Journal of Neuroscience, July 15, 1999, 19(14):6068-6078

Increased Anxiety and Impaired Pain Response in Puromycin-Sensitive Aminopeptidase Gene-Deficient Mice Obtained by a Mouse Gene-Trap Method

Tomoharu Osada^{1, 2}, Shiro Ikegami¹, Keiko Takiguchi-Hayashi¹, Yukiko Yamazaki¹, Yuko Katoh-Fukui¹, Toru Higashinakagawa¹, Yoshiyuki Sakaki², and Takashi Takeuchi¹

¹ Mitsubishi Kasei Institute of Life Sciences, Tokyo,194-8511, Japan, and ² Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

A mouse mutation, termed goku, was generated by a gene-trap strategy. goku homozygous mice showed dwarfism, a marked increase in anxiety, and an analgesic effect. Molecular analysis indicated that the mutated gene encodes a puromycin-sensitive aminopeptidase (Psa; EC 3.4.11.14), whose functions in vivo are unknown. Transcriptional arrest of the Psa gene and a drastic decrease of aminopeptidase activity indicated that the function of Psa is disrupted in homozygous mice. Together with the finding that the Psa gene is strongly expressed in the brain, especially in the striatum and hippocampus, these results suggest that the Psa gene is required for normal growth and the behavior associated with anxiety and pain.

Key words: puromycin-sensitive aminopeptidase; anxiety; analgesia; dwarfism; gene trap; enkephalins

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19146068-11$05.00/0

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