Claims
- 1. A transgenic mouse comprising a disruption in a mGluR4 gene.
- 2. A transgenic mouse comprising a disruption in a mGluR4 gene, wherein there is no native expression of mGluR4 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 comprising a disruption in an mGluR4b gene, wherein the transgenic mouse exhibits an abnormality in a stimulus processing test.
- 6. The transgenic mouse of claim 4, wherein the stimulus processing test is associated with sensorimotor gating.
- 7. The transgenic mouse of claim 4, wherein the transgenic mouse exhibits increased prepulse inhibition of a startle reflex relative to a wild-type mouse.
- 8. The transgenic mouse of claim 4, wherein the transgenic mouse is more resistant to the induction of schizophrenic-like symptoms as compared to a wild-type mouse.
- 9. The transgenic mouse of claim 8, wherein the transgenic mouse exhibits higher prepulse inhibition as compared to a wild-type mouse.
- 10. The transgenic mouse of claim 4, wherein the transgenic mouse exhibits a decreased sound response as compared to a wild-type mouse.
- 11. The transgenic mouse of claim 10, wherein the decreased sound response is at high intensity sound levels.
- 12. The transgenic mouse of claim 11, wherein the decreased sound response is at high intensity sound levels is consistent with an anxiolytic-like effect.
- 13. A method of producing a transgenic mouse comprising a disruption in a mGluR4 gene, the method comprising:
(a) providing a murine stem cell comprising a disruption in a mGluR4 gene; and (b) introducing the murine stem cell into a pseudopregnant mouse, wherein the pseudopregnant mouse gives birth to a transgenic mouse.
- 14. The transgenic mouse produced by the method of claim 13.
- 15. A targeting construct comprising:
(a) a first polynucleotide sequence homologous to at least a first portion of a mGluR4 gene; (b) a second polynucleotide sequence homologous to at least a second portion of a mGluR4 gene; and (c) a selectable marker.
- 16. A cell comprising a disruption in a mGluR4 gene, the disruption produced using the targeting construct of claim 15.
- 17. A cell derived from the transgenic mouse of claim 2.
- 18. A cell comprising a disruption in a mGluR4 gene.
- 19. The cell of claim 18, wherein the cell is a stem cell.
- 20. The cell of claim 19, wherein the stem cell is an embryonic stem cell.
- 21. The cell of claim 20, wherein the embryonic stem cell is a murine cell.
- 22. A method of identifying an agent that modulates prepulse inhibition, the method comprising:
(a) contacting a test agent with mGluR4; and (b) determining whether the agent modulates mGluR4.
- 23. A method of identifying an agent that modulates stimulus processing, the method comprising:
(a) contacting a test agent with a mGluR4; and (b) determining whether the agent modulates the mGluR4.
- 24. A method of identifying a antipsychotic agent, the method comprising:
(a) contacting a test agent with a mGluR4; and (b) determining whether the agent modulates the mGluR4.
- 25. A method of identifying an agent that modulates stimulus processing, the method comprising:
(a) administering a test agent to an animal comprising a disruption in mGluR4; and (b) determining whether the agent modulates stimulus processing of the animal.
- 26. A method of identifying a potential therapeutic agent for the treatment of abnormal behavior, the method comprising:
(a) administering the potential therapeutic agent to a transgenic mouse comprising a disruption in a mGluR4 gene; and (b) determining whether the potential therapeutic agent modulates the abnormal behavior.
- 27. The method of claim 26, wherein the abnormal behavior comprises schizophrenia, psychosis, or mood disorders.
- 28. A method of identifying an antipsychotic agent, the method comprising:
(a) administering the potential antipsychotic agent to a transgenic mouse comprising a disruption in a mGluR4 gene; and (b) determining whether the agent modulates stimulus processing of the animal.
- 29. A method of identifying a potential therapeutic agent for the treatment of a psychotic disorder, the method comprising:
(a) contacting the potential therapeutic agent with mGluR4; (b) determining whether the agent modulates mGluR4, wherein modulation of mGluR4 identifies a potential therapeutic agent for the treatment of psychosis or mood disorder.
- 30. A method of identifying a potential therapeutic agent for the treatment of schizophrenia, the method comprising:
(a) contacting the potential therapeutic agent with a mGluR4; (b) determining whether the agent modulates the mGluR4 molecule, wherein modulation of the mGluR4 molecule identifies a potential therapeutic agent for the treatment of schizophrenia.
- 31. A method of evaluating a potential therapeutic agent capable of affecting a condition associated with a mutation in a mGluR4 gene, the method comprising:
(a) administering the potential therapeutic agent to a transgenic mouse comprising a disruption in a mGluR4 gene; and (b) evaluating the effects of the agent on the transgenic mouse.
- 32. A method of evaluating a potential therapeutic agent capable of affecting a condition associated with a mutation in a mGluR4 gene, the method comprising:
(a) contacting the potential therapeutic agent with mGluR4; (b) evaluating the effects of the agent on the mGluR4.
- 33. A method of identifying an agent capable of modulating psychosis, 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 interacts with the first and second preparations, wherein interaction with the second preparation in the absence of interaction with the first preparation identifies a potential therapeutic agent for the treatment of psychosis.
- 34. A therapeutic agent for treating psychosis or schizophrenia, wherein the agent modulates mGluR4.
- 35. A therapeutic agent for treating psychosis or schizophrenia, wherein the agent is an agonist or antagonist of mGluR4.
- 36. A pharmaceutical composition comprising mGluR4.
- 37. A method of preparing a pharmaceutical composition for a condition associated with a function of mGluR4, the method comprising:
(a) identifying a compound that modulates mGluR4; (b) synthesizing the identified compound; and (c) incorporating the compound into a pharmaceutical carrier.
- 38. The method of claim 37, wherein the condition is a psychotic disorder.
- 39. The method of claim 38, wherein the disorder is schizophrenia.
- 40. Phenotypic data associated with a transgenic mouse comprising a disruption in a mGluR4 gene, wherein the phenotypic data is in an electronic database.
RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Application No. 60/324,768 filed Sep. 24, 2001, the entire contents of which are incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60324768 |
Sep 2001 |
US |