Unequal expression of allelic kainate receptor GluR7 mRNAs in human brains

We describe here the first example of an exonic polymorphism that affects t he primary structure of a human ionotropic glutamate receptor. The human ka inate receptor GluR7 gene contains a thymine (T)/guanine (G) nucleotide var iation that determines a serine or alanine at position 310 in the extracell ular region of GluR7 receptor subunits. Our finding contrasts with a previo us report that suggested that GluR7 transcripts were RNA-edited at this sit e. Whole-cell patch-clamp recordings did not detect differences in receptor activation and desensitization between the human GluR7 receptor isoforms e xpressed in HEK-293 cells. Analysis of 41 tissue samples obtained from 30 h uman brains revealed expression level differences between GluR7 alleles exp ressed in the same brain. The expression level of the allelic GluR7 mRNAs d iffered in 27 samples from 1.2- to 12.7-fold. Unequal expression level of a llelic mRNAs is characteristic for genes that are affected by genomic impri nting or that contain mutations. Genomic imprinting in most cases is conser ved between human and mice. However, we did not detect unequal expression o f allelic GluR7 mRNAs in mice. Our results are important for future studies that explore a potential role or roles for GluR7 receptors in the brain an d for neurological disorders.