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Published September 1, 1991 | Published
Journal Article Open

Molecular cloning and chromosomal localization of one of the human glutamate receptor genes

Abstract

Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are classified on the basis of their activation by different agonists. The agonists kainate and ɑ-amino-3-hydroxy-5-methyl-4-isoxasolepropionic acid define a class of glutamate receptors termed kainate receptors. We have isolated and sequenced a human glutamate receptor (GluHI) cDNA and determined the chromosomal localization of its gene. The DNA sequence of GluHI would encode a 907-amino acid protein that has a 97% identity to one of the rodent kainate receptor subunits. Many of the changes between the predicted amino acid sequence of GluHI and the most similar rodent kainate receptor (GluRI) occur in a region of the protein encoded in rodents by an alternatively spliced exon. The extreme conservation between the human and rat kainate receptor subunits suggests that a similar gene family will encode human kainate receptors. The GluHI mRNA is widely expressed in human brain. The human gene encoding the GluHI subunit is located at 5q33. While the GluHI gene is not located near a chromosomal region associated with any human neurogenetic disorders, the homologous region on mouse chromosome 11 contains the sites of five neurologic mutations.

Additional Information

© 1991 National Academy of Sciences. Contributed by Leroy Hood, May 10, 1991. The authors thank Lee Kozar, Tim Hunkapiller, and Ben Koop for assistance and advice on the computer analyses. We thank Kai Wang and Eric Lai for use of their human cosmid library. We thank Muriel Davisson (The Jackson Laboratory) for providing current information on the homologous mouse regions and Carol Miller (Alzheimer's Disease Research Center, University of Southern California School of Medicine, funded by National Institute on Aging Grant S-P50- AGO5142) for providing the human autopsy material. We also thank Chris Casey for expert technical assistance and the Biology Division offices for preparation of this manuscript. We acknowledge Henry Lester, Joan Kobori, Tim Hunkapiller, and Sally Orr for critical reading of the manuscript. C.P. received support from National Institute of Neurological and Communicative Disorders and Stroke Clinical Investigator Development Award NS 01163-44. J.R.K. is supported by grants from the Public Health Service (R29 H600037-01), the American Health Assistance Foundation, and the Alzheimer Association.

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