Claims
- 1. An isolated nucleic acid molecule encoding a polypeptide comprising an amino acid sequence that is at least 75% identical to SEQ ID NO: 2 or 4, or the complement of said nucleic acid molecule.
- 2. The isolated nucleic acid molecule of claim 1, wherein said nucleic acid molecule hybridizes under stringent conditions to a nucleic acid sequence complementary to a nucleic acid molecule comprising the sequence of nucleotides of SEQ ID NO: 1 or 3, or the complement of said nucleic acid molecule.
- 3. The isolated nucleic acid molecule of claim 1, wherein said nucleic acid molecule encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 2 or 4 or an amino acid sequence comprising one or more conservative substitutions in the amino acid sequence of SEQ ID NO: 2 or 4.
- 4. The nucleic acid molecule of claim 1, wherein said nucleic acid molecule encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 2 or 4, or the complement of said nucleic acid molecule.
- 5. The nucleic acid molecule of claim 1, wherein said nucleic acid molecule comprises the sequence of nucleotides of SEQ ID NO: 1 or 3, or the complement of said nucleic acid molecule.
- 6. The nucleic acid molecule of claim 1, wherein said nucleic acid molecule has the nucleotide sequence of a cDNA.
- 7. The nucleic acid molecule of claim 1, wherein said nucleic acid molecule comprises contiguous nucleotides encoding the amino acid sequence WEKPI (SEQ ID NO: 5).
- 8. An isolated nucleic acid molecule, wherein said nucleic acid molecule:
(a) encodes a polypeptide having the amino acid sequence of SEQ ID NO: 2; and (b) comprises contiguous nucleotides encoding the amino acid sequences. WEKPI (SEQ ID NO: 5); or the complement of said nucleic acid molecule.
- 9. A nucleic acid molecule less than 100 nucleotides in length and comprising at least 6 contiguous nucleotides of SEQ ID NO: 1 or a complement thereof.
- 10. A nucleic acid vector comprising the nucleic acid molecule of claim 1.
- 11. A host cell comprising the isolated nucleic acid molecule of claim 1.
- 12. An isolated polypeptide at least 80% identical to a polypeptide selected from the group consisting of:
a) a polypeptide comprising an amino acid sequence of SEQ ID NO: 2 or 4; b) a fragment of a polypeptide comprising an amino acid sequence of SEQ ID NO: 2 or 4, wherein the fragment comprises at least 6 contiguous amino acids of SEQ ID NO: 2; c) a derivative of a polypeptide comprising an amino acid sequence of SEQ ID NO: 2 or 4; d) an analog of a polypeptide comprising an amino acid sequence of SEQ ID NO: 2 or 4; e) a homolog of a polypeptide comprising an amino acid sequence of SEQ ID NO: 2 and 4; and f) a naturally occurring allelic variant of a polypeptide comprising an amino acid sequence of SEQ ID NO: 2 or 4, wherein the polypeptide is encoded by a nucleic acid molecule that hybridizes to a nucleic acid molecule of SEQ ID NO: 1 or 3, under stringent conditions.
- 13. The polypeptide of claim 12, wherein the polypeptide, or fragment thereof,
a) binds to a glycoprotein hormone receptor; b) binds to a LGR orphan G-protein-coupled receptor; c) binds to a glycoprotein hormone; or d) binds to a cystine knot protein.
- 14. The polypeptide of claim 12, wherein the polypeptide, or fragment thereof, is glycosylated at one or more sites.
- 15. The polypeptide of claim 12, wherein the polypeptide, or fragment thereof, is not glycosylated.
- 16. The polypeptide of claim 12, wherein the polypeptide, or fragment thereof, comprises a cystine knot domain.
- 17. A protein multimer comprising a first polypeptide according to claim 12, and a second polypeptide.
- 18. A protein multimer comprising an ARP polypeptide and a second polypeptide.
- 19. The protein multimer according to claim 17 or 18, wherein said second polypeptide is identical to the first polypeptide.
- 20. The protein multimer according to claim 17, wherein said second polypeptide is an apha glycoprotein subunit.
- 21. The protein multimer according to claim 18, wherein said second polypeptide is an beta glycoprotein subunit.
- 22. The protein multimer according to claim 17 or 18, wherein said second polypeptide is a cystine knot protein.
- 23. The protein multimer according to claim 17, wherein said second polypeptide comprises the amino acid sequence of SEQ ID NO: 18.
- 24. The protein multimer according to claim 17 or 18, wherein said protein multimer is a dimer
- 25. An antibody that selectively binds to the polypeptide of claim 12, and fragments, homologs, analogs, and derivatives of said antibody.
- 26. An antibody that selectively binds to the protein multimer of claim 17 or 18, and fragments, homologs, analogs, and derivatives of said antibody.
- 27. A method of producing a BRP polypeptide, said method comprising the step of culturing the host cell of claim 11 under conditions in which the nucleic acid molecule is expressed.
- 28. A method of detecting the presence of the polypeptide of claim 12 in a sample, comprising contacting the sample with a compound that selectively binds to the polypeptide of claim 12 and determining whether the compound bound to the polypeptide of claim 12 is present in the sample.
- 29. A method of detecting the presence of a nucleic acid molecule of claim 1 in a sample, the method comprising contacting the sample with a nucleic acid probe or primer that selectively binds to the nucleic acid molecule and determining whether the nucleic acid probe or primer bound to the nucleic acid molecule of claim 1 is present in the sample.
- 30. A method for modulating the activity of the polypeptide of claim 12, the method comprising contacting a cell sample comprising the polypeptide of claim 12 with a compound that binds to said polypeptide in an amount sufficient to modulate the activity of the polypeptide.
- 31. A method of treating or preventing a reproductive disorder in a subject, the method comprising administering to a subject method comprising administering to a subject in need thereof a therapeutic selected from the group consisting of:
a) a ARP/BRP nucleic acid; b) a ARP/BRP polypeptide and c) a ARP/BRP antibody; wherein said therapeutic is administered in an amount sufficient to treat or prevent said reproductive disorder in said subject.
- 32. A method of treating or preventing a reproductive disorder in a subject, the method comprising administering to a subject method comprising administering to a subject in need thereof a therapeutic comprising a protein multimer of claim 17 or 18 wherein said therapeutic is administered in an amount sufficient to treat or prevent said reproductive disorder in said subject.
- 33. A pharmaceutical composition comprising a therapeutically or prophylactically effective amount of a therapeutic selected from the group consisting of:
a) a ARP/BRP nucleic acid; b) a ARP/BRP polypeptide and c) a ARP/BRP antibody and a pharmaceutically acceptable carrier.
- 34. A pharmaceutical composition comprising a therapeutically or prophylactically effective amount of a therapeutic selected from the group consisting of the protein multimer of claim 17 or 18 and a pharmaceutically acceptable carrier.
- 35. A kit comprising in one or more containers, comprising a therapeutically or prophylactically effective amount of the pharmaceutical composition of claim 33 or 34.
- 36. A method for screening for a modulator of activity or of latency or predisposition to a reproductive disorder, said method comprising:
a) administering a test compound to a test animal at increased risk for a pathology associated with the polypeptide of claim 1, wherein said test animal recombinantly expresses a ARP/BRP polypeptide; b) measuring the activity of said polypeptide in said test animal after administering the compound of step (a); and c) comparing the activity of said protein in said test animal with the activity of said polypeptide in a control animal not administered said polypeptide, wherein a change in the activity of said polypeptide in said test animal relative to said control animal indicates the test compound is a modulator of latency of, or predisposition to, a reproductive disorder.
- 37. The method of claim 35, wherein said test animal is a recombinant test animal that expresses a test protein transgene or expresses said transgene under the control of a promoter at an increased level relative to a wild-type test animal, and wherein said promoter is not the native gene promoter of said transgene.
- 38. A method for determining the presence of or predisposition to a reproductive disorder in a subject, the method comprising:
a) measuring the amount of a ARP/BRP polypeptide or ARP/BRP multimer in a sample from the subject; and b) comparing the amount of said polypeptide in step (a) to the amount of the polypeptide present in a control sample, wherein an alteration in the level of the polypeptide or multimer in step (a) as compared to the control sample indicates a disease condition.
- 39. A method for determining the presence of or predisposition t o a reproductive disorder in a subject, the method comprising:
a) measuring the amount of a ARP/BRP nucleic acid in a sample from the mammalian subject; and b) comparing the amount of said nucleic acid in step (a) to the amount of the nucleic acid present in a control sample, wherein an alteration in the level of the nucleic acid in step (a) as compared to the control sample indicates a disease condition.
- 40. A method for expressing an ARP/BRP polyppetide as a product if an endogenous gene in a cell, wherein the polypeptide is expressed at a modified level ina comparison to the wild type cell, the method comprising;
(a) transfecting the cell with a DNA constuct, the DNA constrict comprising a transcription regulatory element in operative connection to the endogenous gene, thereby producing a recombinant cell and/or (b) transfecting the cell with a DNA constuct, the DNA constrict comprising a amplifiable gene and a DNA targeting sequence capable of inserting the amplifiable gene in operative connection to the endogenous gene, thereby producing a recombinant cell a (c) culturing the recombinant cell, and if desired, selecting cells containing multiple copies of the endogenous gene.
RELATED APPLICATIONS
[0001] This application claims priority from Applications U.S. Ser. No. 60/,225,035 filed Aug. 11, 2000 and U.S. Ser. No. 09/851,465 filed May 8, 2001, which claims priority from U.S. Ser. No. 60/202,724 filed May 8, 2000, which are incorporated by reference in their entirety.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60202724 |
May 2000 |
US |
|
60225035 |
Aug 2000 |
US |
Continuations (1)
|
Number |
Date |
Country |
Parent |
09851465 |
May 2001 |
US |
Child |
09927876 |
Aug 2001 |
US |