Mutant rat strain lacking D-amino-acid oxidase.
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.
Konno
Ryuichi
R
Center for Medical Science, International University of Health and Welfare, Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan. konno-r@iuhw.ac.jp
Okamura
Tadashi
T
Kasai
Noriyuki
N
Summer
Karl H
KH
Niwa
Akira
A
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003605:D-Amino-Acid Oxidase / Q000172:deficiency* / Q000235:genetics; D017930:Genes, Reporter; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000201:enzymology; D051379:Mice; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014020:Tissue Extracts / Q000378:metabolism; D014158:Transcription, Genetic; D018911:Trinucleotide Repeats
D012333:RNA, Messenger; D014020:Tissue Extracts; D003605:D-Amino-Acid Oxidase