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Mutant rat strain lacking D-amino-acid oxidase
Ryuichi Konno1, Tadashi Okamura, Noriyuki Kasai
1Center for Medical Science, International University of Health and Welfare, Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan. konno-r@iuhw.ac.jp
Amino Acids
|August 22, 2008
Summary
Rats lacking D-amino-acid oxidase (DAO) due to a gene deletion were identified. This finding is crucial for understanding DAO
Area of Science:
- Biochemistry
- Genetics
- Neuroscience
Background:
- D-amino-acid oxidase (DAO) is implicated in schizophrenia.
- Previous studies indicated low DAO gene expression in LEA rats.
Purpose of the Study:
- Investigate the cause of absent DAO activity in LEA/SENDAI rats.
- Determine the role of TAA repeats in DAO gene expression.
- Establish LEA/SENDAI rats as a model for schizophrenia research.
Main Methods:
- Sequencing of the 5'-upstream region of the DAO gene.
- Reporter vector assays in cell lines (COS-1, NRK-52E, CCL-PK1).
- Electrophoretic mobility-shift assays (EMSA).
Main Results:
- LEA/SENDAI rats exhibit no DAO activity, enzyme protein, or mRNA.
- A deletion of one triplet in a 15 TAA repeat sequence was found in the DAO gene's 5'-upstream region.
- DAO gene promoter activity is dependent on the number of TAA repeats (15 or 14 repeats show high activity, 13 show weak activity).
- Proteins in nuclear extracts bind to TAA repeat sequences.
Conclusions:
- TAA repeats in the DAO gene's upstream region are critical for its expression.
- The deletion in LEA/SENDAI rats significantly impairs DAO gene transcription.
- LEA/SENDAI rats lacking DAO are a valuable model for studying the flavoenzyme's role in schizophrenia.
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