Gene structure and chromosomal localization of the mouse NMDA receptor channel subunits

Multiple ε subunits are major determinants of the diversity of the N-methyl-D-aspartate (NMDA) receptor channel. The four ε subunit mRNAs exhibit distinct expression patterns in the brain. In an attempt to elucidate the molecular basis of selective and characteristic expression of the NMDA receptor channel subunits, we have isolated the gene encoding the mouse NMDA receptor ε3 subunit and have determined its structural organization. The ε3 subunit gene spans 17.5 kb and consists of 14 exons. The major transcription start site is 439 bp upstream of the ATG initiation codon as determined by primer extension and S1 nuclease protection analyses. Two polyadenylation sites are 397 (or 398) and 402 bp downstream of the termination codon. The 5'-flanking region of the ε3 subunit gene contains GC-rich segments including consensus sequences for binding of the transcription factors Sp1 and EGR-1. The murine chromosomal locations of the five NMDA receptor channel subunits, the ε1 (Grin2a), ε2 (Grin2b), ε3 (Grin2c), ε4 (Grin2d) and ζ1 (Grin1) subunits, were determined using an interspecific backcross mapping panel derived from crosses of [(C57BL/6J x M. spretus) F₁ x C57BL/6J] mice. Each of these genes mapped to a single chromosome location. The mapping results assigned the five loci to five different mouse autosomes, indicating that they have become well dispersed among mouse chromosomes.