D-serine is now considered to be an endogenous co-agonist of the NMDA receptor in mammalian brain. To obtain insight into the molecular mechanisms underlying D-serine metabolism and function, we explored transcripts that are responsive to D-serine in the neocortex of the 8-day-old infant rat by a differential cloning technique, RNA arbitrarily primed PCR. We isolated a novel D-serine inducible transcript, D-serine-responsive transcript-2 (dsr-2), that was exclusively expressed in the brain. Sequence analysis of the corresponding cDNAs to the transcript revealed that the dsr-2 mRNA consists of 7199 nucleotides with an open reading frame encoding 111 amino acids. The dsr-2 gene was located on the reverse strand within an intron of the neurexin-3alpha gene, mapped to rat chromosome 6q24-31. The regional distribution of the basal expression of dsr-2 and its ontogenic changes in the brain closely correlated with those of free D-serine and of NMDA receptor R2B subunit mRNA, but were somewhat different from those of the neurexin-3alpha transcript. These findings suggest that dsr-2 may be involved in D-serine metabolism and/or function, and in the interactions between D-serine, NMDA receptor and neurexin-3alpha, in mammalian brain.
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