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Behaviors of Mutant Mice Lacking d-Amino-Acid Oxidase Activity

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D-Amino Acids

Abstract

d-Amino-acid oxidase (DAO) catalyzes oxidative deamination of d-amino acids, including d-serine. DAO is present in the brain, liver, and kidney of higher animals. A large amount of d-serine is known to be present in the mammalian brains. d-Serine is a co-agonist of N-methyl-d-aspartate-subtype glutamate receptors (NMDARs) and potentiates NMDAR activity. NMDARs are involved in many physiological and pathological processes, and an abnormal NMDAR activity can thus have a severe effect on normal functioning. For instance, NMDAR hypofunction is considered one of the causes of schizophrenia, and over-excitation of NMDARs causes neuronal cell death, which can lead to amyotrophic lateral sclerosis. Therefore, d-serine is considered to be deeply involved in both diseases. Since DAO degrades d-serine, DAO is also associated with these illnesses. Accordingly, mutant mice lacking DAO activity have been attracting much attention of the researchers. In this article, we review currently available studies on behaviors of DAO mutant mice, especially those associated with schizophrenia. As of yet, accumulated behavioral data have not been necessarily consistent to draw a clear conclusion, the reasons for which are considered and discussed.

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References

  • Almond SL, Fradley RL, Armstrong EJ, Heavens RB, Rutter AR, Newman RJ, Chiu CS, Konno R, Hutson PH, Brandon NJ (2006) Behavioral and biochemical characterization of a mutant mouse strain lacking d-amino acid oxidase activity and its implications for schizophrenia. Mol Cell Neurosci 32:324–334

    Article  CAS  PubMed  Google Scholar 

  • Chumakov I, Blumenfeld M, Guerassimenko O, Cavarec L, Palicio M et al (2002) Genetic and physiological data implicating the new human gene G72 and the gene for d-amino acid oxidase in schizophrenia. Proc Natl Acad Sci USA 99:13675–13680

    Google Scholar 

  • Contreras PC (1990) d-Serine antagonized phencyclidine- and MK-801-induced stereotyped behavior and ataxia. Neuropharmacology 29:291–293

    Article  CAS  PubMed  Google Scholar 

  • Ferraris DV, Tsukamoto T (2011) Recent advances in the discovery of d-amino acid oxidase inhibitors and their therapeutic utility in schizophrenia. Curr Pharm Des 17:103–111

    Article  CAS  PubMed  Google Scholar 

  • Gustafson EC, Morgans CW, Tekmen M, Sullivan SJ, Esguerra M, Konno R, Miller RF (2013) Retinal NMDA receptor function and expression are altered in a mouse lacking d-amino acid oxidase. J Neurophysiol 110:2718–2726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hashimoto A, Nishikawa T, Hayashi T, Fujii N, Harada K, Oka T, Takahashi K (1992) The presence of free d-serine in rat brain. FEBS Lett 296:33–36

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto A, Nishikawa T, Konno R, Niwa A, Yasumura Y, Oka T, Takahashi K (1993) Free d-serine, d-aspartate and d-alanine in central nervous system and serum in mutant mice lacking d-amino acid oxidase. Neurosci Lett 152:33–36

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto A, Yoshikawa M, Niwa A, Konno R (2005) Mice lacking d-amino acid oxidase activity display marked attenuation of stereotypy and ataxia induced by MK-801. Brain Res 1033:210–215

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto A, Konno R, Yano H, Yoshikawa M, Tamaki R, Matsumoto H, Kobayashi H (2008) Mice lacking d-amino acid oxidase activity exhibit marked reduction of methamphetamine-induced stereotypy. Eur J Pharmacol 586:221–225

    Article  CAS  PubMed  Google Scholar 

  • Javitt DC, Zukin SR (1991) Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 148:1301–1308

    Article  CAS  PubMed  Google Scholar 

  • Kakegawa W, Miyoshi Y, Hamase K, Matsuda S, Matsuda K, Kohda K, Emi K, Motohashi J, Konno R, Zaitsu K, Yuzaki M (2011) d-Serine regulates cerebellar LTD and motor coordination through the δ2 glutamate receptor. Nat Neurosci 14:603–611

    Article  CAS  PubMed  Google Scholar 

  • Konno R, Yasumura Y (1983) Mouse mutant deficient in d-amino acid oxidase activity. Genetics 103:277–285

    CAS  PubMed  PubMed Central  Google Scholar 

  • Konno R, Sasaki M, Asakura S, Fukui K, Enami J, Niwa A (1997) d-Amino-acid oxidase is not present in the mouse liver. Biochim Biophys Acta 1335:173–181

    Google Scholar 

  • Konno R, Okamura T, Kasai N, Summer KH, Niwa A (2009) Mutant rat strain lacking d-amino-acid oxidase. Amino Acids 37:367–375

    Article  CAS  PubMed  Google Scholar 

  • Konno R, Hamase K, Maruyama R, Zaitsu K (2010) Mutant mice and rats lacking d-amino acid oxidase. Chem Biodivers 7:1450–1458

    Article  CAS  PubMed  Google Scholar 

  • Krebs HA (1935) Metabolism of amino-acids: deamination of amino-acids. Biochem J 29:1620–1644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Labrie V, Wong AH, Roder JC (2012) Contributions of the d-serine pathway to schizophrenia. Neuropharmacology 62:1484–1503

    Article  CAS  PubMed  Google Scholar 

  • Labrie V, Clapcote SJ, Roder JC (2009a) Mutant mice with reduced NMDA-NR1 glycine affinity or lack of d-amino acid oxidase function exhibit altered anxiety-like behaviors. Pharmacol Biochem Behav 91:610–620

    Article  CAS  PubMed  Google Scholar 

  • Labrie V, Duffy S, Wang W, Barger SW, Baker GB, Roder JC (2009b) Genetic inactivation of d-amino acid oxidase enhances extinction and reversal learning in mice. Learn Mem 16:28–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Labrie V, Wang W, Barger SW, Baker GB, Roder JC (2010) Genetic loss of d-amino acid oxidase activity reverses schizophrenia-like phenotypes in mice. Genes Brain Behav 9:11–25

    Article  CAS  PubMed  Google Scholar 

  • Maekawa M, Watanabe M, Yamaguchi S, Konno R, Hori Y (2005) Spatial learning and long-term potentiation of mutant mice lacking d-amino-acid oxidase. Neurosci Res 53:34–38

    Article  CAS  PubMed  Google Scholar 

  • Mitchell J, Paul P, Chen HJ, Morris A, Payling M, Falchi M, Habgood J, Panoutsou S, Winkler S, Tisato V, Hajitou A, Smith B, Vance C, Shaw C, Mazarakis ND, de Belleroche J (2010) Familial amyotrophic lateral sclerosis is associated with a mutation in d-amino acid oxidase. Proc Natl Acad Sci U S A 107:7556–7561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyoshi Y, Hamase K, Okamura T, Konno R, Kasai N, Tojo Y, Zaitsu K (2011) Simultaneous two-dimensional HPLC determination of free d-serine and d-alanine in the brain and periphery of mutant rats lacking d-amino-acid oxidase. J Chromatogr B 879:3184–3189

    Google Scholar 

  • Mothet JP, Parent AT, Wolosker H, Brady RO Jr, Linden DJ, Ferris CD, Rogawski MA, Snyder SH (2000) d-Serine is an endogenous ligand for the glycine site of the N-methyl-d-aspartate receptor. Proc Natl Acad Sci USA 97:4926–4931

    Google Scholar 

  • Rais R, Thomas AG, Wozniak K, Wu Y, Jaaro-Peled H, Sawa A, Strick CA, Engle SJ, Brandon NJ, Rojas C, Slusher BS, Tsukamoto T (2012) Pharmacokinetics of oral d-serine in d-amino acid oxidase knockout mice. Drug Metab Dispos 40:2067–2073

    Google Scholar 

  • Santangelo RM, Acker TM, Zimmerman SS, Katzman BM, Strong KL, Traynelis SF, Liotta DC (2012) Novel NMDA receptor modulators: an update. Expert Opin Ther Pat 22:1337–1352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sasabe J, Miyoshi Y, Suzuki M, Mita M, Konno R, Matsuoka M, Hamase K, Aiso S (2012) d-Amino acid oxidase controls motoneuron degeneration through d-serine. Proc Natl Acad Sci USA 109:627–632

    Google Scholar 

  • Sasaki M, Konno R, Nishio M, Niwa A, Yasumura Y, Enami J (1992) A single-base-pair substitution abolishes d-amino-acid oxidase activity in the mouse. Biochim Biophys Acta 1139:315–318

    Article  CAS  PubMed  Google Scholar 

  • Schweimer JV, Coullon GS, Betts JF, Burnet PW, Engle SJ, Brandon NJ, Harrison PJ, Sharp T (2014) Increased burst-firing of ventral tegmental area dopaminergic neurons in d-amino acid oxidase knockout mice in vivo. Eur J Neurosci 40:2999–3009

    Article  PubMed  Google Scholar 

  • Swerdlow NR, Weber M, Qu Y, Light GA, Braff DL (2008) Realistic expectations of prepulse inhibition in translational models for schizophrenia research. Psychopharmacology (Berl) 199:331–388

    Google Scholar 

  • Verrall L, Burnet PW, Betts JF, Harrison PJ (2010) The neurobiology of d-amino acid oxidase and its involvement in schizophrenia. Mol Psychiatry 15:122–137

    Article  CAS  PubMed  Google Scholar 

  • Wake K, Yamazaki H, Hanzawa S, Konno R, Sakio H, Niwa A, Hori Y (2001) Exaggerated responses to chronic nociceptive stimuli and enhancement of N-methyl-d-aspartate receptor-mediated synaptic transmission in mutant mice lacking d-amino-acid oxidase. Neurosci Lett 297:25–28

    Google Scholar 

  • Wolosker H, Sheth KN, Takahashi M, Mothet JP, Brady RO Jr, Ferris CD, Snyder SH (1999) Purification of serine racemase: biosynthesis of the neuromodulator d-serine. Proc Natl Acad Sci USA 96:721–725

    Google Scholar 

  • Wolosker H, Dumin E, Balan L, Foltyn VN (2008) d-Amino acids in the brain: d-serine in neurotransmission and neurodegeneration. FEBS J 275:3514–3526

    Google Scholar 

  • Yamanaka M, Miyoshi Y, Ohide H, Hamase K, Konno R (2012) d-Amino acids in the brain and mutant rodents lacking d-amino-acid oxidase activity. Amino Acids 43:1811–1821

    Article  CAS  PubMed  Google Scholar 

  • Zhang M, Ballard ME, Basso AM, Bratcher N, Browman KE, Curzon P, Konno R, Meyer AH, Rueter LE (2011) Behavioral characterization of a mutant mouse strain lacking d-amino acid oxidase activity. Behav Brain Res 217:81–87

    Article  CAS  PubMed  Google Scholar 

  • Zhao W, Konno R, Zhou XJ, Yin M, Wang YX (2008) Inhibition of d-amino-acid oxidase activity induces pain relief in mice. Cell Mol Neurobiol 28:581–591

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, 324-8501, Tochigi, Japan

    Hiroaki Sakaue, Hiroko Ohide, Masahiro Yamanaka & Ryuichi Konno

Authors
  1. Hiroaki Sakaue
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  2. Hiroko Ohide
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  3. Masahiro Yamanaka
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  4. Ryuichi Konno
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Correspondence to Hiroaki Sakaue .

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Editors and Affiliations

  1. Department of Applied Molecular Biosciences Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan

    Tohru Yoshimura

  2. Department of Psychiatry and Behavioral Sciences Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

    Toru Nishikawa

  3. Laboratory of Biomolecular Science Department of Pharmaceutical Life Sciences, Kitasato University, Tokyo, Japan

    Hiroshi Homma

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Sakaue, H., Ohide, H., Yamanaka, M., Konno, R. (2016). Behaviors of Mutant Mice Lacking d-Amino-Acid Oxidase Activity. In: Yoshimura, T., Nishikawa, T., Homma, H. (eds) D-Amino Acids. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56077-7_4

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