The Journal of Neuroscience, December 15, 2000, 20(24):9025-9033
Unequal Expression of Allelic Kainate Receptor GluR7 mRNAs in
Human Brains
Hans H.
Schiffer1,
Geoffrey T.
Swanson1,
Elizier
Masliah2, and
Stephen F.
Heinemann1
1 Molecular Neurobiology Laboratory, Salk Institute for
Biological Studies, La Jolla, California 92037, and
2 Department of Neurosciences, University of California,
San Diego, La Jolla, California 92039-0624
We describe here the first example of an exonic polymorphism that
affects the primary structure of a human ionotropic glutamate receptor.
The human kainate receptor GluR7 gene contains a thymine (T)/guanine
(G) nucleotide variation that determines a serine or alanine at
position 310 in the extracellular region of GluR7 receptor subunits.
Our finding contrasts with a previous report that suggested that GluR7
transcripts were RNA-edited at this site. Whole-cell patch-clamp
recordings did not detect differences in receptor activation and
desensitization between the human GluR7 receptor isoforms expressed in
HEK-293 cells. Analysis of 41 tissue samples obtained from 30 human
brains revealed expression level differences between GluR7 alleles
expressed in the same brain. The expression level of the allelic GluR7
mRNAs differed in 27 samples from 1.2- to 12.7-fold. Unequal expression
level of allelic mRNAs is characteristic for genes that are affected by
genomic imprinting or that contain mutations. Genomic imprinting in
most cases is conserved between human and mice. However, we did not detect unequal expression of 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 and for neurological disorders.
Key words:
kainate receptor; GluR7; polymorphism; allele expression; genomic imprinting; RNA editing
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