The Salk Institute for Biological Studies

Other

Duke University

The Salk Institute

Stephen Fox Heinemann

James Richard Boulter

James Warner Patrick

Evan Samuel Deneris

Robert M Duvoisin

Marc Charles Ballivet

John Gerard Connolly

Eden Deer Heinemann

Keiji Wada

David S Johnson

Ana Belen Elgoyhen

Daniel Jay Goldman

Bernhard Bettler

Michael Hollmann

Jan Egebejerg Jensen

Barbara D Boss

W Maxwell Cowan

James O McNamara

Scott W Rogers

Robert Michael Duvoisin

Hans H Schiffer

The present invention relates to a family of neuronal nicotinic acetylcholine receptors comprised of neuronal agonist and non-agonist binding subunits, and DNA sequences encoding such subunits. These novel neuronal nicotinic acetylcholine receptor subunits include the agonist binding subunits alpha2, alpha3, alpha4, and alpha5, plus non-agonist binding subunits beta2, beta3 and beta4. Representative cDNA clones that contain the DNA sequences of the invention have been deposited with the American Type Culture Collection for patent purposes.

Neuronal nicotinic acetylcholine receptor compositions

Provided are methods for determining the predisposition of a subject to a mood disorder by determining in a biological sample of a subject, the presence of a kainate receptor subunit GluR7 allelic genotype or allelic phenotype associated with predisposition to a mood disorder. The allelic genotype is homozygosity for a thymine containing nucleotide at position 928 (928T/T) or homozygosity for a guanine containing nucleotide position 928 (928G/G). In addition, a predominant expression of one GluR7 allele over the other allele in a heterozygous individuals also predicts predisposition to a mood disorder. The present invention also includes a method of treating or preventing a mood disorder and methods for identifying a compound useful for treatment. Transgenic non-human animals that express only a particular human GluR7 allele at nucleotide position 928 also are provided as a model of a human mood disorder.

Kainate receptor subunit GLUR7 polymorphisms for determining predispositions to recurrent unipolar and bipolar II depressive disorders

The present invention provides isolated nucleic acids encoding alpha9 nicotinic acetylcholine receptor subunit and receptor subunit protein encoded thereby. Also provided are vectors containing the invention nucleic acids, host cells transformed therewith, alpha9 nicotinic acetylcholine receptor subunit and functional nicotinic acetylcholine receptors comprising at least one alpha9 subunit expressed recombinantly in such host cells as well as transgenic non-human mammals that express the invention receptor subunit and mutants thereof. Receptors of the invention comprise at least one alpha9 nicotinic acetylcholine subunit and form cationic channels activated by acetylcholine, but blocked by nicotine and muscarine. The invention also provides methods for identifying compounds that modulate the ion channel activity of the functional invention receptors containing at least one invention subunit.

Cloning and expression of a novel acetylcholine-gated ion channel receptor subunit

Neuronal nicotinic acetylcholihne receptor compositions

Methods of identifying modulators of alpha9, a novel acetylcholine-gated

Cloning and expression of a novel acetylcholine-gated ion channel

The present invention discloses novel DNAs that encode proteins having electrophysiological and pharmacological properties characteristic of glutamate receptors. The glutamate receptors are exemplified by proteins encoded by representative cDNA clones GluR1, GluR2, GluR3, GluR4, GluR5, GluR6 and GluR7, fragments thereof, and functional combinations of these glutamate receptor proteins and/or fragments. DNA sequences from the cDNA clones for GluR1, GluR2, GluR3, GluR4 and GluR5 are especially useful as probes, thus enabling those skilled in the art to identify, without undue experimentation, other members of the L-glutamate receptor family.

Glutamate receptor compositions and method

The present invention discloses a new neuronal nicotinic acetylcholine receptor subunit, .beta.4. The new subunit can form functional combinations with other neuronal nicotinic acetylcholine receptor subunits, including, but not limited to, alpha2, alpha3, alpha4 and beta2. A cDNA clone containing the DNA sequences that encode the novel receptor subunit of the invention has been deposited with the American Type Culture Collection for patent purposes.

Recombinantly produced .beta.4 neuronal nicotinic acetylcholine receptor

The present invention discloses novel DNAs that encode proteins having electrophysiological and pharmacological properties characteristic of glutamate receptors. The glutamate receptors are exemplified by proteins encoded by representative cDNA clones GluR1, GluR2, GluR3, GluR4, GluR5, GluR6 and GluR7, fragments thereof, and functional combinations of these glutamate receptor proteins and/or fragments. DNA sequences from the cDNA clones for GluR1, GluR2, GluR3, GluR5 and GluR5 are especially useful as probes, thus enabling those skilled in the art to identify, without undue experimentation, other members of the L-glutamate receptor family.

Glutamate receptor antibodies

Neuronal nicotinic acetylcholine receptor assay

A method of screening a subject for a central nervous system disorder caused by autoimmune disease (e.g., an inflammatory seizure disorder) comprises a sample from the subject and then detecting the presence or absence of anti-glutamate receptor autoantibodies (e.g., anti-GluR3 glutamate receptor autoantibodies) in the biological sample. The presence of such autoantibodies indicates the subject is afflicted with a central nervous system disorder caused by autoimmune disease. Methods of treating such disease by reducing the number of autoantibodies available to bind to glutamate receptors in the subject are also disclosed.

Methods of detecting disorders of the central nervous system by

DNA encoding neuronal nicotinic acetylcholine receptor compositions

Isolated nucleic acids encoding glutamate receptor protein

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La Jolla, CA, United States of America

Stephen Fox Heinemann