Claims
- 1. A method for screening for modulators of expression of hnf4α from the hnf4α P2 promoter region, said method comprising the steps of
a) contacting a putative modulator with a transcription reporter system comprising a reporter gene under control of an hnf4α P2 promoter region corresponding to nucleotides 1 to 1447 of SEQ ID No. 1 or a fragment of nucleotides 1 to 1447 of SEQ ID No. 1, and b) assaying for a change in expression of the reporter gene.
- 2. The screening method according to claim wherein the fragment of nucleotides 1 to 1447 of SEQ ID No. 1 comprises an hnf1α binding site.
- 3. The method according to claim 2, wherein the hnf1α binding site comprises nucleotides 79 to 93 of SEQ ID No. 3 or a fragment thereof to which hnf1α is capable of binding.
- 4. The method according to claim 1 wherein the change in expression of the reporter gene is an increase in expression.
- 5. A modulator of expression of hnf4α identified by a method according to claim 1.
- 6. A method for treating diabetes in an animal, said method comprising the step of modulating the expression of hnf4α in pancreatic cells by administering to said animal an effective dose of a modulator according to claim 5.
- 7. The method according to claim 6 wherein the modulation is effected via the hnf4α P2 promoter corresponding to nucleotides 1 to 1447 of SEQ ID No. 1.
- 8. The method according to claim 6, wherein administration of the modulator results in an increase in expression of hnf4α.
- 9. The method according to claim 6, wherein the modulation is effected via a hnf1α binding site corresponding to nucleotides 79 to 93 of SEQ ID No. 3 or a fragment thereof to which hnf1α is capable of binding.
- 10. The method according to 6, wherein the animal is a mammal.
- 11. The method according to claim 10, where the mammal is a human being.
- 12. The method according to claim 6, wherein the animal suffers from maturity onset diabetes of the young (MODY).
- 13. The method according to claim 12, wherein the animal suffers from MODY1.
- 14. The method according to claim 6, wherein the animal suffers from type 2 diabetes.
- 15. Use of a modulator according to claim 5 for treating diabetes in an animal.
- 16. Use of a modulator according to claim 5 for treating MODY in an animal.
- 17. Use of a modulator according to claim 5 for treating type 2 diabetes in an animal.
- 18. Use according to any of claims 15 to 17 wherein the animal is a mammal.
- 19. Use according to claim 18 wherein the animal is a human being.
- 20. A method for screening for diabetes in an animal, said method comprising:
analyzing a nucleic acid molecule obtained from said animal to detect a mutation in the hnf4α P2 promoter region as shown in SEQ ID No. 1, wherein the mutation results in a lesser degree of expression of hnf4α and, is indicative of a propensity for diabetes.
- 21. The method according to claim 20, wherein the hnf4α P2 promoter region corresponds to nucleotides 1 to 1447 of SEQ ID No. 1.
- 22. The method according to claim 20 wherein the hnf4α P2 promoter region comprises the region corresponding to nucleotides 79 to 93 of SEQ ID No. 1.
- 23. The method according to claim 22, wherein the mutation is a mutation of a G to an A in the position corresponding to position 80 in SEQ ID No. 3.
Priority Claims (1)
Number |
Date |
Country |
Kind |
EP 01610085.1 |
Aug 2001 |
EP |
|
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority under 35 U.S.C. §119 of European application EP 01610085.1 filed Aug. 17, 2001, and of U.S. provisional application No. 60/325,271 filed Sep. 27, 2001, the contents of which are hereby incorporated by reference.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60325271 |
Sep 2001 |
US |