Claims
- 1. A method of determining predisposition of a subject to a mood disorder, said method comprising 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.
- 2. The method of claim 1, wherein said 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).
- 3. The method of claim 2, wherein said 928T/T homozygosity is associated with recurrent unipolar depressive disorder.
- 4. The method of claim 2, wherein said 928 G/G homozygosity is associated with bipolar II depressive disorder.
- 5. The method of claim 1, wherein said allelic phenotype is homozygosity for a serine at amino acid position 310 (310 Ser/Ser) or homozygosity for an alanine at position 310 (310 Ala/Ala).
- 6. The method of claim 5, wherein said 310Ser/Ser homozygosity is associated with recurrent unipolar depressive disorder.
- 7. The method of claim 5, wherein said 310 Ala/Ala homozygosity is associated with bipolar II depressive disorder.
- 8. A method of determining predisposition to a mood disorder in a subject having a T/G heterozygosity at nucleotide position 928 in the GluR7 gene, said method comprising determining in a biological sample of the subject, a predominance in the expression of either the T allele or the G allele.
- 9. The method of claim 8, wherein said predominance of expression of the T allele is associated with predisposition to recurrent unipolar depressive disorder.
- 10. The method of claim 8, wherein said predominance of expression of the G allele is associated with predisposition to bipolar II depressive disorder.
- 11. The method of claim 8 where said predominance of expression is about 1.2 fold or greater.
- 12. The method of claim 8, wherein said predominance is determined by comparing the level of expression of said T and G alleles in GluR7 mRNA.
- 13. The method of claim 8, wherein said predominance is determined by comparing the level of expression of GluR7 protein., wherein said T allele results in a GluR7 protein having serine at position 310 and said G allele results in a GluR7 protein having an alanine at position 310.
- 14. A kit for determining predisposition of a subject to a mood disorder, said kit comprising at least one reagent specific for detecting a kainate receptor subunit GluR7 allele associated with a mood disorder.
- 15. The kit of claim 14, wherein said specific reagent is an oligonucleotide.
- 16. The kit of claim 14, wherein said specific reagent is an antibody
- 17. The kit of claim 15, wherein said oligonucleotide hybridizes specifically to the human GluR7 gene or MRNA when the nucleotide at position 928 is a thymine.
- 18. The kit of claim 15, wherein said oligonucleotide hybridizes specifically to the human GluR7 gene or mRNA when the nucleotide at position 928 is a guanine.
- 19. The kit of claim 15, wherein said oligonucleotide hybridizes specifically to the human GluR7 gene or MRNA when the nucleotide at position 928 is a thymine.
- 20. The kit of claim 16, wherein said antibody binds specifically to the human GluR7 protein when the amino acid at position 310 is an alanine.
- 21. The kit of claim 16, wherein said antibody binds specifically to the human GluR7 protein when the amino acid at position 310 is a serine.
- 22. A method of treating or preventing a mood disorder effected by abnormal GluR7 receptor subunit activity or function in a subject, said method comprising administering to said subject an effective amount of a compound that modulates GluR7 receptor subunit activity or function.
- 23. The method of claim 22, wherein said compound modifies the activity or function of the GluR7 receptor subunit having a thymine at nucleotide position 928 of the human GluR7 receptor subunit.
- 24. The method of claim 22, wherein said individual is homozygous for the human GluR7 allele having a thymine at nucleotide position 928.
- 25. The method of claim 22, wherein said compound modifies the activity or function of the GluR7 receptor subunit having a guanine at nucleotide position 928 of the human GluR7 receptor subunit.
- 26. The method of claim 22, wherein said individual is homozygous for the human GluR7 allele having a thymine at nucleotide position 928
- 27. The method of claim 23, wherein said mood disorder is recurrent unipolar depressive disorder.
- 28. The method of claim 25, wherein said mood disorder bipolar II depressive disorder.
- 29. The method of claim 22, wherein said compound is identified by
a) incubating a cell expressing a GluR7 receptor subunit with the compound under conditions sufficient to permit the compound to interact with cell; and b) comparing the activity or function of said GluR7 receptor subunit incubated in the presence of the compound with the activity or function of a GluR7 receptor subunit in the absence of the compound, thereby identifying a compound that modulates GluR7 receptor subunit activity or function.
- 30. The method of claim 29, wherein said compound is selected from the group consisting of peptides, peptidomimetics, polypeptides, pharmaceuticals, biological agents, antibodies, neurotropic agents, and combinatorial compound libraries.
- 31. The method of claim 29, wherein said cell is a neuronal cell or a glial cell.
- 32. A transgenic non-human animal as a model of a human mood disorder, said transgenic animal having a genome comprising a disruption of the endogenous GluR7 genes and insertion of a functional human GluR7 gene.
- 33. The transgenic animal of claim 32, wherein said GluR7 gene has a thymine at nucleotide position 928.
- 34. The transgenic animal of claim 32, wherein said GluR7 gene has a guanine nucleotide position 928.
- 35. The transgenic animal of claim 32, wherein said disruption comprises the insertion of a transgene comprising a selectable marker sequence.
- 36. The transgenic animal of claim 32, wherein said animal is murine.
STATEMENT AS TO FEDERALLY SPONSORED RESEARCH
[0001] This invention was made with Government support under the National Institutes of Health. The government may have certain rights in the invention.