Claims
- 1. A method for identifying a modulator of HDL-levels in an animal, comprising:
(a) contacting a cell with a test compound wherein said cell expresses an ABCA1-gene and comprises an LXR site, wherein said test compound is a modulator of LXR-activity and wherein said contacting occurs under conditions facilitating ABCA1-gene expression, and (b) determining an increase in said ABCA1-gene expression as a result of said contacting, wherein an increase in ABCA1-gene expression indicates ability to modulate HDL-levels in an animal thereby identifying said test compound as a modulator of HDL-levels.
- 2. The method of claim 1 wherein said test compound increases LXR-activity.
- 3. The method of claim 1 wherein said increase in ABCA1-gene expression is an increase in transcription of said ABCA1-gene.
- 4. The method of claim 1 wherein said increase in ABCA1-gene expression is an increase in translation of a protein encoded by said ABCA1-gene.
- 5. The method of claim 1 wherein said cell is a mammalian cell.
- 6. The method of claim 1 wherein said cell is a recombinant cell engineered to express said ABCA1-gene.
- 7. The method of claim 6 wherein expression of ABCA1-gen does not occur absent said engineering.
- 8. The method of claim 1 wherein said cell is a recombinant cell engineered to contain said LXR site.
- 9. The method of claim 8 wherein the cell does not contain said LXR site absent said engineering.
- 10. The method of claim 5 wherein said mammalian cell is a fibroblast.
- 11. The method of claim 5 wherein said mammalian cell is a macrophage.
- 12. The method of claim 5 wherein said mammalian cell is a mouse cell.
- 13. The method of claim 5 wherein said mammalian cell is a human cell.
- 14. The method of claim 1 wherein said ABCA1-gene encodes a mammalian ABCA1.
- 15. The method of claim 1 wherein said ABCA1-gene encodes a protein having an amino acid sequence with at least 50% identity to the amino acid sequence of SEQ ID NO: 5.
- 16. The method of claim 1 wherein said ABCA1-gene encodes a protein having an amino acid sequence with at least 85% identity to the amino acid sequence of SEQ ID NO: 5.
- 17. The method of claim 1 wherein said ABCA1-gene encodes a protein having an amino acid sequence with at least 90% identity to the amino acid sequence of SEQ ID NO: 5.
- 18. The method of claim 1 wherein said ABCA1-gene encodes a protein having an amino acid sequence with at least 95% identity to the amino acid sequence of SEQ ID NO: 5.
- 19. The method of claim 1 wherein said ABCA1-gene encodes a protein that comprises the amino acid sequence of SEQ ID NO: 5.
- 20. The method of claim 1 wherein said ABCA1-gene encodes a protein that comprises amino acid residues 1-60 of SEQ ID NO: 5.
- 21. The method of claim 1 wherein said LXR is LXRα.
- 22. The method of claim 1 wherein said test compound is an oxysterol.
- 23. The method of claim 1 wherein said increase in ABCA1-gene expression is the occurrence of ABCA1-gene expression where said expression does not occur absent said contacting.
- 24. A method for identifying an HDL-modulating agent, comprising administering to an animal an agent having ABCA1-modulating activity in the method of claim 1 and determining a change in HDL-levels in said animal following said administering.
- 25. The method of claim 24 wherein said agent was first identified as having ABCA1-modulating activity in the method of claim 1.
- 26. A method of treating a condition in an animal comprising administering to an animal afflicted therewith a therapeutically effective amount of an agent that has HDL-level modulating activity in the method of claim 1 and wherein said condition is a member selected from the group consisting of a lower than normal HDL-l vel, a higher than normal triglyceride level, inflammation, diabetes, obesity and cardiovascular disease.
- 27. The method of claim 26 wherein said agent was first identified as having HDL-level modulating activity using the method of claim 1.
- 28. The method of claim 26 wherein said condition is coronary artery disease.
- 29. The method of claim 26 wherein said inflammation is a member selected from the group consisting of rheumatoid arthritis, systemic lupus erythematosis (SLE), hypo-thyroidism, hyperthyroidism and inflammatory bowel disease.
- 30. The method of claim 26 wherein said condition is diabetes.
- 31. The method of claim 26 wherein said condition is obesity.
- 32. The method of claim 26 wherein said animal is a human being.
- 33. A method of increasing HDL-levels in an animal having lower than normal HDL-level comprising administering to said animal an effective amount of an agent that has HDL-level modulating activity in the method of claim 1.
- 34. The method of claim 33 wherein said agent was first identified as having HDL-level modulating activity using the method of claim 1.
Parent Case Info
[0001] This application is a divisional of U.S. application Ser. No. 09/654,323, filed Sep. 1, 2000, and claims priority of Provisional Application No. 60/213,958 filed Jun. 23, 2000, and U.S. Utility application Ser. No. 09/526,193, filed Mar. 15, 2000, which claims priority from U.S. Provisional Application No. 60/124,702, filed Mar. 15, 1999; U.S. Provisional Application No. 60/138,048, filed Jun. 8, 1999; U.S. Provisional Application No. 60/139,600, filed Jun. 17, 1999; and U.S. Provisional Application No. 60/151,977, filed Sep. 1, 1999.
Provisional Applications (5)
|
Number |
Date |
Country |
|
60213958 |
Jun 2000 |
US |
|
60124702 |
Mar 1999 |
US |
|
60138048 |
Jun 1999 |
US |
|
60139600 |
Jun 1999 |
US |
|
60151977 |
Sep 1999 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
09654323 |
Sep 2000 |
US |
Child |
10745377 |
Dec 2003 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
09526193 |
Mar 2000 |
US |
Child |
10745377 |
Dec 2003 |
US |