Cloning of a D-serine-regulated transcript dsr-1 from the rat cerebral cortex

To obtain insight into the molecular mechanisms underlying the metabolism and functions of endogenous d-serine, we have explored d-serine-regulated transcripts in the neocortex of the infant rat treated with acute d-serine administration by using an RNA fingerprinting technique. Cloning and sequence analysis of the corresponding cDNAs to the identified transcripts have revealed that the dsr-1 (d-serine responsive transcript-1) mRNA is presumed to contain a novel sequence at the 5'-region, while the 631-base nucleotide sequence of its 3'-end is identical with that of rat M9.2 mRNA encoding a subunit of vacuolar type proton-ATPase. The predicted two open reading frames and their deduced amino acid sequences suggest that the dsr-1 product has a membrane spanning domain. The dsr-1 transcript was detected as a single band around 2.1 kb on the Northern blot. RT-PCR analyses have indicated that the dsr-1 transcript is expressed predominantly in the brain, lung, and testis, and that acute intraperitoneal injection of d-serine significantly upregulates dsr-1 expression in the neocortex 3 and 15 h later without affecting the levels of the M9.2 gene transcript. These results suggest that dsr-1 products may be involved in the d-serine-related metabolic or signaling pathways in mammalian brains.