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Mutant rat strain lacking D-amino-acid oxidase.
Amino Acids 37, 367-375 (2009)
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
D-Amino-acid oxidase; Rat mutant; Promoter; Triplet repeats; Schizophrenia; d-aspartate receptor; free d-serine; nmda receptors; gene; schizophrenia; localization; glycine; repeat; brain; mouse
ISSN (print) / ISBN
0939-4451
e-ISSN
1438-2199
Journal
Amino Acids
Quellenangaben
Volume: 37,
Issue: 2,
Pages: 367-375
Publisher
Springer
Publishing Place
Berlin [u.a.]
Non-patent literature
Publications
Reviewing status
Peer reviewed