Cloning and expression of the human NMDA receptor subunit NR3B in the adult human hippocampus.

The mammalian genome encodes seven different NMDA receptor subunits. All of these subunits have been cloned in the human except for NR3B. Here, we have successfully obtained two full-length clones of human NR3B using a PCR-based cloning approach. The open reading frame of the consensus sequence contains 3129 nucleotides translating into 1043 amino acids. The overall polypeptide sequence identity with mouse NR3B is 74.9%, which is lower than for the other six NMDA receptor subunits. In particular, the translated part of exon 9 is only 37.8% identical between human and mouse. The GRIN3B gene, which encodes human NR3B, maps to chromosome 19p13.3, between WDR18 and C19orf6 (membralin). Human NR3B is encoded by nine exons, as in mouse NR3B, and exon-intron boundaries are conserved between the species. However, exon 9 is substantially longer in the human. In situ hybridization data shows that NR3B mRNA is expressed in the human hippocampal formation (CA1-CA4 and dentate gyrus) and adjacent neocortex. The expression of NR3A mRNA was restricted to the dentate gyrus and layers IV and V of the neocortex. Our results may have implications for the understanding of the role of NMDA receptors for physiological and pathological processes in these forebrain regions.