GENE STRUCTURE AND CHROMOSOMAL LOCALIZATION OF THE MOUSE NMDA RECEPTOR-CHANNEL SUBUNITS

Multiple epsilon subunits are major determinants of the diversity of t he N-methyl-D-aspartate (NMDA) receptor channel. The four epsilon subu nit mRNAs exhibit distinct expression patterns in the brain. In an att empt 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 epsilon 3 subunit and have dete rmined its structural organization. The epsilon 3 subunit gene spans 1 7.5 kb and consists of 14 exons. The major transcription start site is 439 bp upstream of the ATG initiation codon as determined by primer e xtension and S1 nuclease protection analyses. Two polyadenylation site s are 397 (or 398) and 402 bp downstream of the termination codon. The 5'-flanking region of the epsilon 3 subunit gene contains GC-rich seg ments including consensus sequences for binding of the transcription f actors Sp1 and EGR-1. The murine chromosomal locations of the five NMD A receptor channel subunits, the epsilon 1 (Grin2a), epsilon 2 (Grin2b ), epsilon 3 (Grin2c), epsilon 4 (Grin2d) and zeta 1 (Grin1) subunits, were determined using an interspecific backcross mapping panel derive d from crosses of [(C57BL/6JXM. spretus)F-1 X C57BL/6J] mice. Each of these genes mapped to a single chromosome location. The mapping result s assigned the five loci to five different mouse autosomes, indicating that they have become well dispersed among mouse chromosomes.