Claims
- 1. A targeting construct comprising:
(a) a first polynucleotide sequence homologous to at least a first portion of an FPR-RS4 gene; (b) a second polynucleotide sequence homologous to at least a second portion of the FPR-RS4 gene; and (c) a selectable marker.
- 2. A method of producing a targeting construct, the method comprising:
(a) providing a first polynucleotide sequence homologous to at least a first portion of an FPR-RS4 gene; (b) providing a second polynucleotide sequence homologous to at least a second portion of the FPR-RS4 gene; (c) providing a selectable marker; and (d) inserting the first sequence, second sequence, and selectable marker into a vector to produce the targeting construct.
- 3. A cell comprising a disruption in an FPR-RS4 gene.
- 4. The cell of claim 3, wherein the cell is a murine cell.
- 5. The cell of claim 4, wherein the murine cell is an embryonic stem cell.
- 6. A non-human transgenic animal comprising a disruption in an FPR-RS4 gene.
- 7. The non-human transgenic animal of claim 6, wherein the transgenic animal is a mouse.
- 8. A cell derived from the transgenic mouse of claim 7.
- 9. A method of producing a transgenic mouse comprising a disruption in an FPR-RS4 gene, the method comprising:
(a) introducing the targeting construct of claim 1 into a cell; (b) introducing the cell into a blastocyst; (c) implanting the resulting blastocyst into a pseudopregnant mouse, wherein said pseudopregnant mouse gives birth to a chimeric mouse; and (d) breeding the chimeric mouse to produce the transgenic mouse.
- 10. A method of identifying an agent that modulates the expression or function of an FPR-RS4 gene, the method comprising:
(a) providing a non-human transgenic animal comprising a disruption in an FPR-RS4 gene; (b) administering an agent to the non-human transgenic animal; and (c) determining whether the expression or function of the disrupted FPR-RS4 gene in the non-human transgenic animal is modulated.
- 11. A method of identifying an agent that modulates the expression or function of an FPR-RS4 gene, the method comprising:
(a) providing a cell comprising a disruption in an FPR-RS4 gene; (b) contacting the cell with the agent; and (c) determining whether the expression or function of the FPR-RS4 gene is modulated.
- 12. The method of claim 11, wherein the cell is derived from the non-human transgenic animal of claim 6.
- 13. An agent identified by the method of claim 10 or claim 11.
- 14. A transgenic mouse comprising a disruption in an FPR-RS4 gene, wherein there is no significant expression of the FPR-RS4 gene in the transgenic mouse.
- 15. A transgenic mouse comprising a homozygous disruption in an FPR-RS4 gene, wherein the transgenic mouse exhibits increased anxiety.
- 16. The transgenic mouse of claim 15, wherein the increased anxiety is characterized by decreased time spent in a central region of an open field test.
- 17. A transgenic mouse comprising a homozygous disruption in an FPR-RS4 gene, wherein the transgenic mouse exhibits impaired motor coordination or balance or ataxia.
- 18. The transgenic mouse of claim 17, wherein the transgenic mouse exhibits a decrease in performance on an accelerating rotarod.
- 19. The transgenic mouse of claim 18, wherein the transgenic mouse falls off the accelerating rotarod at a lower speed relative to a wild-type mouse.
- 20. A transgenic mouse comprising a homozygous disruption in an FPR-RS4 gene, wherein the transgenic mouse exhibits a decreased susceptibility to seizure.
- 21. The transgenic mouse of claim 20, wherein the mouse exhibits seizure-like responses at a higher dose of Metrazol, relative to a wild-type mouse.
- 22. A cell derived from the transgenic mouse of claim 14.
- 23. A method of identifying an agent that ameliorates a phenotype associated with a disruption in an FPR-RS4 gene, the method comprising:
(a) administering an agent to a transgenic mouse comprising a disruption in an FPR-RS4 gene; and (b) determining whether the agent ameliorates at least one of the following phenotypes: increased anxiety, impaired motor coordination or balance, ataxia, or decreased susceptibility to seizure.
- 24. An agent identified by the method of claim 23.
- 25. An agonist or antagonist of FPR-RS4.
- 26. Phenotypic data associated with a transgenic mouse comprising a disruption in an FPR-RS4 gene, wherein the phenotypic data is in an electronic database.
- 27. A method of treating anxiety, the method comprising administering to a subject in need a therapeutically effective amount of FPR-RS4.
- 28. A method of treating impaired motor coordination, impaired balance, or ataxia, the method comprising administering to a subject in need a therapeutically effective amount of FPR-RS4.
- 29. A method of identifying an agent that ameliorates anxiety, the method comprising:
(a) administering an agent to the transgenic mouse of claim 15; and (b) determining whether the agent has an affect on anxiety in the transgenic mouse.
- 30. A method of identifying an agent that ameliorates impaired motor coordination, impaired balance, or ataxia, the method comprising:
(a) administering an agent to the transgenic mouse of claim 17; and (b) determining whether the agent has an affect on motor coordination, balance or ataxia in the transgenic mouse.
- 31. A method of evaluating treatments for anxiety, the method comprising:
(a) administering a therapeutic agent to the transgenic mouse of claim 15; and (b) determining the in vivo effects of the agent on anxiety level in the transgenic mouse.
- 32. A method of evaluating treatments for impaired motor coordination, impaired balance, or ataxia, the method comprising:
(a) administering a therapeutic agent to the transgenic mouse of claim 17; and (b) determining the in vivo effects of the agent on motor coordination, balance, or ataxia in the transgenic mouse.
- 33. A method of identifying an agent that inhibits the activity or function of FPR-RS4, the method comprising:
(a) providing a cell expressing FPR-RS4; (b) contacting the cell with an agent; and (c) determining whether the agent inhibits the activity or function of FPR-RS4, wherein the agent has an affect on seizure susceptibility.
- 34. A pharmaceutical composition comprising a FPR-RS4 protein.
RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Application No. 60/251,817, filed Dec. 6, 2000, and U.S. Provisional Application No. 60/311,056, filed Aug. 8, 2001, the entire contents of each are incorporated herein by reference.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60251817 |
Dec 2000 |
US |
|
60311056 |
Aug 2001 |
US |