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Mutant rat strain lacking d-amino-acid oxidase

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Abstract

d-Amino-acid oxidase (DAO) is known to be associated with schizophrenia. Since the expression of DAO gene had been reported to be very low in LEA rats, we examined LEA/SENDAI rats in detail. These rats did not have DAO activity, enzyme protein or mRNA encoding this enzyme. Sequencing of the 5′-upstream region of the DAO gene revealed the deletion of one triplet in the 15 TAA repeats approximately 700-bp upstream of the transcription start point. A 1.3-kb upstream fragment containing the TAA repeats and the transcription start point was inserted into a reporter vector and was transfected into COS-1, NRK-52E and CCL-PK1 cells. Although the fragments containing 15 or 14 repeats had high promoter activity, the fragment containing 13 repeats had very weak activity. Electrophoretic mobility-shift assays showed that the nuclear extracts from COS-1 and COS-7 cells had proteins that bound to the oligonucleotides containing the TAA repeats. These results suggest that the TAA repeats are important for expression of the DAO gene. The LEA/SENDAI rats lacking DAO would be a useful tool for the investigations aimed at the elucidation of the relationships between this flavoenzyme and schizophrenia.

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Acknowledgments

We thank Professor Jun Yanagisawa, University of Tsukuba, for providing us with the COS-1 cells. We also thank Mr. D. Lee for his advice in preparing the manuscript. A part of this work was supported by grants from the Asahi Glass Foundation and the Seki Minato Foundation.

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Authors and Affiliations

  1. Center for Medical Science, International University of Health and Welfare, Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan

    Ryuichi Konno & Akira Niwa

  2. Division of Animal Models, Department of Infectious Diseases, Research Institute, International Medical Center of Japan, Tokyo, Japan

    Tadashi Okamura

  3. Institute for Animal Experimentation, Tohoku University Graduate School of Medicine, Sendai, Japan

    Noriyuki Kasai

  4. Institute of Toxicology, GSF-National Research Center for Environment and Health, Neuherberg, Germany

    Karl H. Summer

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  1. Ryuichi Konno
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  2. Tadashi Okamura
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  3. Noriyuki Kasai
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  4. Karl H. Summer
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  5. Akira Niwa
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Correspondence to Ryuichi Konno.

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Konno, R., Okamura, T., Kasai, N. et al. Mutant rat strain lacking d-amino-acid oxidase. Amino Acids 37, 367–375 (2009). https://doi.org/10.1007/s00726-008-0163-1

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  • DOI: https://doi.org/10.1007/s00726-008-0163-1

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