Claims
- 1. A transgenic non-human animal having a transgene disrupting or interfering with expression of regulator of G-protein signaling 9 (RGS9), wherein said transgene is chromosomally integrated into germ cells of the animal.
- 2. The transgenic animal of claim 1, wherein the animal is a species of animal selected from murine, bovine, ovine, avian or piscine.
- 3. The transgenic animal of claim 1, wherein said animal is homozygous or heterozygous for said disruption of the endogenous RGS9 gene.
- 4. A transgenic mouse comprising a disruption in the regulator of G-protein signaling 9 (RGS9) gene, wherein the disruption of the RGS9 gene results in an inability of the mouse to produce detectable levels of RGS9.
- 5. The transgenic mouse of claim 4, wherein the disruption results from the introduction of a transgene into the genome by homologous recombination with a DNA targeting construct in an embryonic stem cell such that the targeting construct is stably integrated in the genome of the mouse.
- 6. A method for producing a transgenic mouse exhibiting an inability to produce detectable levels of RGS9, the method comprising:
(a) introducing a transgene comprising a selectable marker sequence into a mouse embryonic stem cell; (b) introducing said mouse embryonic stem cell into a mouse embryo; (c) transplanting said embryo into a pseudopregnant mouse; (d) allowing said embryo to develop to term; and (e) identifying a transgenic mouse whose genome comprises a disruption of the endogenous RGS9 gene, wherein said disruption results in said mouse exhibiting a decreased ability to produce detectable levels of RGS9 as compared to a wild-type mouse.
- 7. A transgenic mouse produced by the method of claim 6, wherein the genome of the mouse comprises a disruption of the endogenous RGS9, wherein the disruption results in the mouse exhibiting a decreased ability to produce detectable levels of RGS9 as compared to a wild-type mouse.
- 8. The method of claim 6, wherein the transgenic mouse is homozygous or heterozygous for the disruption of the endogenous RGS9 gene.
- 9. A method for screening a candidate agent for the ability to modulate dopamine D2-mediated behavior in the transgenic animal of claim 1 comprising:
(a) administering to a first transgenic animal of claim 1 a candidate agent, and (b) comparing dopamine D2-mediated behavior of the first transgenic animal to the dopamine D2-mediated behavior of a second transgenic animal of claim 1 not administered the candidate agent; wherein a difference in dopamine D2-mediated behavior in the first transgenic animal administered the candidate agent compared to the second transgenic animal not administered the candidate agent is indicative of a candidate agent that modifies dopamine D2-mediated behavior.
- 10. The method of claim 9, wherein the dopamine D2-mediated behavior is motor behavior.
- 11. The method of claim 9, wherein the dopamine D2-mediated behavior is drug induced behavior.
- 12. The method of claim 9, wherein the dopamine D2-mediated behavior is weight gain.
- 13. A method for screening a candidate agent for the ability to modulate dopamine D2-mediated behavior comprising comparing the interaction between a RGS protein and a dopamine D2 receptor in the presence of a candidate agent and in the absence of a candidate agent, wherein a difference in the interaction between the RGS protein and the dopamine D2 receptor in the presence of the candidate agent compared to the interaction in the absence of the candidate is indicative of a candidate agent that modifies dopamine D2-mediated behavior.
- 14. The method of claim 13, wherein the interaction between the RGS protein and the dopamine D2 receptor is the binding between the RGS protein and the dopamine D2 receptor.
- 15. A method of modulating a level of dopamine D2-mediated behavior comprising administering to a subject in need of such treatment an agent, wherein the agent modulates the activity of a RGS protein.
- 16. The method of claim 15, wherein the RGS protein is RGS9.
- 17. The method of claim 15, wherein the agent increases the activity of the RGS protein and the level of dopamine D2-mediated behavior is decreased.
- 18. The method of claim 15, wherein the agent decreases the activity of RGS9 and the level of dopamine D2-mediated behavior is increased.
- 19. The method of claim 15, wherein the level of dopamine D2-mediated behavior is in response to a drug.
- 20. The method of claim 19, wherein the drug increases locomotion.
- 21. The method of claim 20, wherein the drug is amphetamine.
- 22. A method of modulating a locomotor response to a drug comprising administering to a subject in need of such treatment an agent, wherein the agent modulates the activity of a RGS protein.
- 23. The method of claim 22, wherein the drug is amphetamine.
- 24. The method of claim 22, wherein the RGS protein is RGS9.
- 25. The method of claim 22, wherein the agent decreases the activity of the RGS protein and the locomoter response is increased.
- 26. A method of treating an abnormal motor behavior following a sensitization of dopamine D2 receptors comprising administering to a subject in need of such treatment an agent, wherein the agent increases the activity of a RGS protein.
- 27. The method of claim 26, wherein the RGS protein is RGS9.
- 28. The method of claim 26, wherein the sensitization of dopamine D2 receptors is achieved by a drug.
- 29. A method of treating weight gain comprising administering to a subject in need of such treatment an agent, wherein the agent increases the activity of a RGS protein.
- 30. The method of claim 29, wherein the RGS protein is RGS9.
RELATED APPLICATION DATA
[0001] This application claims priority under 35 U.S.C. 119(e) to Ser. No. 60/242,656, filed Oct. 23, 2000, herein incorporated by reference in its entirety.
ACKNOWLEDGEMENT OF GOVERNMENT SUPPORT
[0002] This invention was made in part with support under NIH Grant Nos. RO1 AG12288, MH-49176 and GM-29836. The government may have certain rights in this invention.
Provisional Applications (1)
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Number |
Date |
Country |
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60242656 |
Oct 2000 |
US |