Claims
- 1. A transgenic mouse comprising a disruption in an OGR1 gene.
- 2. A transgenic mouse comprising a disruption in an OGR1 gene, wherein there is no native expression of endogenous OGR1 gene.
- 3. The transgenic mouse of claim 2, wherein the disruption is heterozygous.
- 4. The transgenic mouse of claim 2, wherein the disruption is homozygous.
- 5. The transgenic mouse of claim 4, wherein the transgenic mouse exhibits hypoactivity.
- 6. The transgenic mouse of claim 5, wherein the hypoactivity is characterized by a decrease in total distance traveled in an open field test.
- 7. The transgenic mouse of claim 6, wherein the total distance traveled is consistent with a symptom associated with human hyperactivity.
- 8. The transgenic mouse of claim 4, wherein the transgenic mouse exhibits a motor abnormality.
- 9. The transgenic mouse of claim 8, wherein the motor abnormality is impaired balance, impaired coordination, or ataxia.
- 10. The transgenic mouse of claim 8, wherein the motor abnormality is characterized by a decrease in fall speed in a rotarod test.
- 11. The transgenic mouse of claim 4, wherein the transgenic mouse exhibits abnormal stimulus processing.
- 12. The transgenic mouse of claim 11, wherein the abnormal stimulus processing is characterized by a decreased startle response.
- 13. The transgenic mouse of claim 11, wherein the abnormal stimulus processing is characterized by enhanced prepulse inhibition.
- 14. The transgenic mouse of claim 13, wherein the prepulse inhibition is consistent with a symptom associated with human schizophrenia.
- 15. A method of producing a transgenic mouse comprising a disruption in an OGR1 gene, the method comprising:
(a) providing a murine stem cell comprising a disruption in an OGR1 gene; and (b) introducing the murine stem cell into a pseudopregnant mouse, wherein the pseudopregnant mouse gives birth to a transgenic mouse.
- 16. The transgenic mouse produced by the method of claim 15.
- 17. A targeting construct comprising:
(a) a first polynucleotide sequence homologous to at least a first portion of an OGR1 gene; (b) a second polynucleotide sequence homologous to at least a second portion of an OGR1 gene; and (c) a selectable marker.
- 18. A cell comprising a disruption in an OGR1 gene, the disruption produced using the targeting construct of claim 17.
- 19. A cell derived from the transgenic mouse of claim 2.
- 20. A cell comprising a disruption in an OGR1 gene.
- 21. The cell of claim 20, wherein the cell is a stem cell.
- 22. The cell of claim 21, wherein the stem cell is an embryonic stem cell.
- 23. The cell of claim 22, wherein the embryonic stem cell is a murine cell.
- 24. A method of identifying an agent that modulates a phenotype selected from the group consisting of hypoactivity, impaired balance, impaired motor coordination, ataxia, decreased startle response, and enhanced prepulse inhibition, the method comprising:
(a) contacting a test agent with OGR1 ; and (b) determining whether the agent modulates OGR1.
- 25. A method of identifying an agent that modulates a phenotype selected from the group consisting of hypoactivity, impaired balance, impaired motor coordination, ataxia, decreased startle response, and enhanced prepulse inhibition, the method comprising:
(a) administering a test agent to an animal exhibiting a phenotype selected from the group consisting of hypoactivity, impaired balance, impaired motor coordination, ataxia, decreased startle response, and enhanced prepulse inhibition; and (b) determining whether the agent modulates the phenotype.
- 26. A method of identifying a potential therapeutic agent for the treatment of schizophrenia, the method comprising:
(a) administering the potential therapeutic agent to a transgenic mouse comprising a disruption in an OGR1 gene; and (b) determining whether the potential therapeutic agent modulates schizophrenia, wherein modulation of schizophrenia identifies a potential therapeutic agent for the treatment of schizophrenia.
- 27. A method of identifying a potential therapeutic agent for the treatment of hyperactivity or impaired balance, the method comprising:
(a) administering the potential therapeutic agent to a transgenic mouse comprising a disruption in an OGR1 gene; and (b) determining whether the potential therapeutic agent modulates hyperactivity or balance, wherein modulation of hyperactivity or balance identifies a potential therapeutic agent for the treatment of hyperactivity or impaired balance.
- 28. A method of identifying a potential therapeutic agent for the treatment of schizophrenia, the method comprising:
(a) contacting the potential therapeutic agent with OGR1; (b) determining whether the agent modulates OGR1, wherein modulation of OGR1 identifies a potential therapeutic agent for the treatment of schizophrenia.
- 29. A method of identifying a potential therapeutic agent for the treatment of hyperactivity or impaired balance, the method comprising:
(a) contacting the potential therapeutic agent with OGR1; (b) determining whether the agent modulates OGR1, wherein modulation of OGR1 identifies a potential therapeutic agent for the treatment of hyperactivity or impaired balance.
- 30. A method of evaluating a potential therapeutic agent capable of affecting a condition or phenotype associated with OGR1, the method comprising:
(a) administering the potential therapeutic agent to a transgenic mouse comprising a disruption in an OGR1 gene; and (b) evaluating the effects of the agent on the transgenic mouse.
- 31. A method of evaluating a potential therapeutic agent capable of affecting a condition or phenotype associated with OGR1, the method comprising:
(a) contacting the potential therapeutic agent with OGR1; (b) evaluating the effects of the agent on the OGR1.
- 32. A method of determining whether an agent modulates OGR1, the method comprising:
(a) providing a first preparation derived from the mouse of claim 2;(b) providing a second preparation derived from a wild-type mouse; (c) contacting a test agent with the first and second preparations; and (d) determining whether the agent modulates the first and second preparations, wherein modulation of the second preparation but not the first preparation indicates that the agent modulates the OGR1.
- 33. A therapeutic agent for treating schizophrenia, wherein the agent modulates OGR1.
- 34. A therapeutic agent for treating schizophrenia, wherein the agent is an antagonist of OGR1.
- 35. A therapeutic agent for treating hyperactivity, wherein the agent modulates OGR1.
- 36. A therapeutic agent for treating hyperactivity, wherein the agent is an antagonist of OGR1.
- 37. A therapeutic agent for improving balance, wherein the agent modulates OGR1.
- 38. A pharmaceutical composition comprising OGR1.
- 39. A method of preparing a pharmaceutical composition for a condition associated with a function of OGR1, the method comprising:
(a) identifying a compound that modulates OGR1; (b) synthesizing the identified compound; and (c) incorporating the compound into a pharmaceutical carrier.
- 40. A method of treating schizophrenia the method comprising administering to a subject in need a therapeutically effective amount of an agent that modulates OGR1.
- 41. A method of treating hyperactivity the method comprising administering to a subject in need a therapeutically effective amount of an agent that modulates OGR1.
- 42. A method of treating impaired balance or improving balance, the method comprising administering to a subject in need a therapeutically effective amount of an agent that modulates OGR1.
- 43. Phenotypic data associated with a transgenic mouse comprising a disruption in an OGR1 gene, wherein the phenotypic data is in an electronic database.
RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Application No. 60/280,320, filed Mar. 29, 2001, and U.S. Provisional Application No. 60/324,615, filed Sep. 24, 2001, the entire contents of which are incorporated herein by reference.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60280320 |
Mar 2001 |
US |
|
60324615 |
Sep 2001 |
US |