WO1996009386B1 - Allelic variation of the serotonin 5ht2c receptor - Google Patents
Allelic variation of the serotonin 5ht2c receptorInfo
- Publication number
- WO1996009386B1 WO1996009386B1 PCT/US1995/012002 US9512002W WO9609386B1 WO 1996009386 B1 WO1996009386 B1 WO 1996009386B1 US 9512002 W US9512002 W US 9512002W WO 9609386 B1 WO9609386 B1 WO 9609386B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- receptor
- serotonin
- antibody
- amino acid
- dna
- Prior art date
Links
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 title claims abstract 36
- 229940076279 Serotonin Drugs 0.000 title claims abstract 18
- 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 title claims abstract 3
- 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 title claims abstract 3
- 102000005962 receptors Human genes 0.000 claims abstract 22
- 108020003175 receptors Proteins 0.000 claims abstract 22
- 229920003013 deoxyribonucleic acid Polymers 0.000 claims abstract 14
- 102000004965 antibodies Human genes 0.000 claims abstract 13
- 108090001123 antibodies Proteins 0.000 claims abstract 13
- 150000001413 amino acids Chemical group 0.000 claims abstract 5
- 235000001014 amino acid Nutrition 0.000 claims 10
- 125000003275 alpha amino acid group Chemical group 0.000 claims 9
- 125000003616 serine group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims 6
- 210000004027 cells Anatomy 0.000 claims 4
- 235000018102 proteins Nutrition 0.000 claims 4
- 102000004169 proteins and genes Human genes 0.000 claims 4
- 108090000623 proteins and genes Proteins 0.000 claims 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N L-serine Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims 3
- 102000035259 5-HT2 receptors Human genes 0.000 claims 2
- 108091005520 5-HT2 receptors Proteins 0.000 claims 2
- 108020001019 DNA Primers Proteins 0.000 claims 2
- 239000003155 DNA primer Substances 0.000 claims 2
- 229920001850 Nucleic acid sequence Polymers 0.000 claims 2
- 230000003321 amplification Effects 0.000 claims 2
- 239000012472 biological sample Substances 0.000 claims 2
- 230000001809 detectable Effects 0.000 claims 2
- 238000001502 gel electrophoresis Methods 0.000 claims 2
- 102000005614 monoclonal antibodies Human genes 0.000 claims 2
- 108010045030 monoclonal antibodies Proteins 0.000 claims 2
- 238000003199 nucleic acid amplification method Methods 0.000 claims 2
- 150000007523 nucleic acids Chemical group 0.000 claims 2
- 108091007521 restriction endonucleases Proteins 0.000 claims 2
- 239000000523 sample Substances 0.000 claims 2
- LZDNBBYBDGBADK-KBPBESRZSA-N (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-(1H-indol-3-yl)propanoic acid Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](N)C(C)C)C(O)=O)=CNC2=C1 LZDNBBYBDGBADK-KBPBESRZSA-N 0.000 claims 1
- 210000004958 Brain cells Anatomy 0.000 claims 1
- 108020004705 Codon Proteins 0.000 claims 1
- DKEXFJVMVGETOO-LURJTMIESA-N Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CN DKEXFJVMVGETOO-LURJTMIESA-N 0.000 claims 1
- MMFKFJORZBJVNF-UWVGGRQHSA-N His-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CN=CN1 MMFKFJORZBJVNF-UWVGGRQHSA-N 0.000 claims 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims 1
- 108010066427 N-valyltryptophan Proteins 0.000 claims 1
- VBKBDLMWICBSCY-IMJSIDKUSA-N Ser-Asp Chemical compound OC[C@H](N)C(=O)N[C@H](C(O)=O)CC(O)=O VBKBDLMWICBSCY-IMJSIDKUSA-N 0.000 claims 1
- 235000018417 cysteine Nutrition 0.000 claims 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims 1
- 230000036425 denaturation Effects 0.000 claims 1
- 238000004925 denaturation Methods 0.000 claims 1
- 238000001514 detection method Methods 0.000 claims 1
- 238000001976 enzyme digestion Methods 0.000 claims 1
- 108010050848 glycylleucine Proteins 0.000 claims 1
- 108010025306 histidylleucine Proteins 0.000 claims 1
- 230000035772 mutation Effects 0.000 claims 1
- 108020004707 nucleic acids Proteins 0.000 claims 1
- 238000003752 polymerase chain reaction Methods 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 abstract 1
Abstract
Isolated DNA encoding the serotonin 5HT2C receptor with serine at amino acid position 23, antibody specific to such a variant receptor and the variant receptor protein itself are used in methods for detecting the presence of an allelic variant of the serotonin 5HT2C gene or receptor.
Claims
1. Isolated DNA encoding the serotonin SW1K receptor, wherein said DNA encodes a serine at amino acid position 23 of said receptor.
2. The isolated DNA of Claim 1 wherein said DNA is in a vector.
3. The isolated DNA of Claim 1 wherein said DNA has the nucleic acid sequence of SEQ ID N0:1.
4. An isolated protein having the amino acid sequence of a serotonin 5HT2Q receptor, wherein said protein has a serine residue at amino acid position 23.
5. The isolated protein of Claim 4 wherein said protein has the amino acid sequence of SEQ ID NQ:2.
6. A method for detecting the presence of DNA encoding an allelic variant of the serotonin 5HT2Q receptor, comprising: isolating DNA encoding the serotonin 5HT2 receptor; amplifying a region of said DNA that encodes amino acid number 23 of the serotonin 5HT2Q receptor; and determining whether said isolated DNA encodes a serine residue at amino acid number 23, wherein a serine residue at amino acid position 23 indicates the presence of an allelic variant of the serotonin 5HT2Q receptor.
7. The method of Claim 6 wherein said amplifying step comprises polymerase chain reaction amplification.
8. The method of Claim 6 wherein said amplification uses DNA primers that insert a new restriction site near the codon that encodes amino acid number 23.
9. The method of Claim 8 wherein said restriction site is cleaved by Hinfl.
10. The method of Claim 8 wherein said DNA primers are SEQ ID NOS: 5 and 6.
11. The method of Claim 6 wherein said determining step further comprises restriction enzyme digestion followed by gel electrophoresis.
12. The method of Claim 6 wherein said determining step includes denaturation of said isolated DNA.
13. The method of Claim 11 wherein said restriction enzyme is Rsa I.
14. The method of Claim 11 wherein said gel electrophoresis is on a Mutation Detection Enhancement gel.
15. The method of Claim 6 wherein said determining step further comprises nucleic acid sequencing of the amplified DNA.
16. An antibody specific for the serotonin 5HT2Q aHelic variant receptor protein wherein said receptor protein has a serine at amino acid position 23.
17. The antibody of Claim 16 wherein said antibody is a monoclonal antibody.
18. A method for detecting the presence of an allelic variant of the serotonin 5HT2Q receptor, comprising: providing a biological sample containing the serotonin 5HT2 receptor; contacting said sample with an antibody which specifically binds to a serotonin 5HT2Q receptor with a serine residue located at amino acid position 23; and detecting the binding of said antibody to said receptor, wherein detectable binding indicates the presence of an allelic form of the serotonin 5HT2Q receptor.
19. The method of Claim 18 wherein said cells are human.
20. The method of Claim 18 wherein said cells are brain cells.
21. The method of Claim 18 wherein said antibody is specific for the extracellular loop of the first transmembrane domain of the serotonin 5HΪ2 receptor.
22. The method of Claim 21 wherein said antibody is a monoclonal antibody.
23. The method of Claim 18 wherein said antibody is labelled.
24. The method of Claim 23 wherein said label is radioactivity.
25. The method of Claim 23 wherein said label is a fluorescent molecule.
26. The method of Claim 18 wherein said antibody is monoclonal.
27. The method of Claim 18 wherein said detecting step further comprises flourescence activated cell sorting.
28. A method for detecting the presence of an allelic variant of the serotonin 5HΪ2 receptor, comprising: providing a biological sample containing the serotonin 5HT2 receptor; contacting said sample with an antibody which specifically binds to a serotonin 5HT2£ receptor having a cysteine residue located at amino acid position 23, and wherein said antibody does not bind a 5HΪ2 receptor having a serine residue at position 23; and detecting the absence of binding of said antibody to said receptor, wherein lack of detectable binding indicates the presence of an allelic form of the serotonin 5HT2 receptor.
29. Host cells containing the vector of Claim 2.
30. An isolated DNA sequence encoding a serotonin 5HT2C receptor containing the amino acid sequence His Leu lie Gly Leu Leu Val Trp Gin Ser Asp lie Ser in the first transmembrane domain.
31. The method of Claim 6 wherein step (c) comprises comparing the amplified region of DNA to SEQ ID N0:1 and determining whether the allelic variant has a cysteine to serine substitution at amino acid 23 by comparing the amplified sequence to SEQ ID N0:1.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP95935029A EP0782618A2 (en) | 1994-09-21 | 1995-09-21 | Allelic variation of the serotonin 5ht 2c? receptor |
| AU37203/95A AU693944B2 (en) | 1994-09-21 | 1995-09-21 | Allelic variation of the serotonin 5HT2C receptor |
| JP8511070A JPH11507802A (en) | 1994-09-21 | 1995-09-21 | Allelic variants of the serotonin 5HT 2C receptor |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/310,271 US5654139A (en) | 1994-09-21 | 1994-09-21 | Allelic variation of the serotonin 5HT2c receptor |
| US08/310,271 | 1994-09-21 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO1996009386A2 WO1996009386A2 (en) | 1996-03-28 |
| WO1996009386A3 WO1996009386A3 (en) | 1996-05-02 |
| WO1996009386B1 true WO1996009386B1 (en) | 1996-07-18 |
Family
ID=23201739
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1995/012002 WO1996009386A2 (en) | 1994-09-21 | 1995-09-21 | Allelic variation of the serotonin 5ht2c receptor |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US5654139A (en) |
| EP (1) | EP0782618A2 (en) |
| JP (1) | JPH11507802A (en) |
| AU (1) | AU693944B2 (en) |
| CA (1) | CA2199470A1 (en) |
| WO (1) | WO1996009386A2 (en) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9507230D0 (en) * | 1995-04-07 | 1995-05-31 | Inst Of Psychiatry | Novel method |
| US6503184B1 (en) | 1997-10-21 | 2003-01-07 | Human Genome Sciences, Inc. | Human tumor necrosis factor receptor-like proteins TR11, TR11SV1 and TR11SV2 |
| JP2001520039A (en) | 1997-10-21 | 2001-10-30 | ヒューマン ジノーム サイエンシーズ， インコーポレイテッド | Human tumor necrosis factor receptor-like proteins, TR11, TR11SV1 and TR11SV2 |
| US6689607B2 (en) | 1997-10-21 | 2004-02-10 | Human Genome Sciences, Inc. | Human tumor, necrosis factor receptor-like proteins TR11, TR11SV1 and TR11SV2 |
| CA2354673A1 (en) * | 1998-12-11 | 2000-06-15 | Children's Hospital Medical Center | Method for determining asthma susceptibility |
| WO2000050459A1 (en) * | 1999-02-24 | 2000-08-31 | Human Genome Sciences, Inc. | Human tumor necrosis factor receptor-like proteins tr11, tr11sv1, and tr11sv2 |
| EP1169344A1 (en) * | 1999-03-12 | 2002-01-09 | Human Genome Sciences, Inc. | 47 human secreted proteins |
| CA2364571A1 (en) | 1999-03-15 | 2000-09-21 | Merck & Co., Inc. | Isoforms of mouse serotonin 5-ht2c receptor |
| CA2365223A1 (en) * | 1999-03-19 | 2000-09-28 | Craig A. Rosen | 46 human secreted proteins |
| CA2368482A1 (en) * | 1999-03-26 | 2000-10-05 | Craig A. Rosen | 50 human secreted proteins |
| JP2003501008A (en) * | 1999-03-26 | 2003-01-14 | ヒューマン ジノーム サイエンシーズ， インコーポレイテッド | 50 human secreted proteins |
| WO2000060057A1 (en) * | 1999-04-05 | 2000-10-12 | Smithkline Beecham Corporation | Rat gpr10 |
| EP1173479A4 (en) * | 1999-04-09 | 2002-11-20 | Human Genome Sciences Inc | 49 human secreted proteins |
| JP2003501011A (en) * | 1999-04-09 | 2003-01-14 | ヒューマン ジノーム サイエンシーズ， インコーポレイテッド | 49 human secreted proteins |
| EP1171467A4 (en) * | 1999-04-27 | 2002-07-31 | Smithkline Beecham Corp | Axor-27, a g-protein coupled receptor |
| EP1173483A4 (en) * | 1999-04-28 | 2002-07-10 | Smithkline Beecham Corp | Acrp30r1m, a homolog of acrp30 |
| US6552017B1 (en) | 1999-06-15 | 2003-04-22 | Bristol-Myers Squibb Pharma Company | Substituted heterocycle fused gamma-carbolines |
| US6713471B1 (en) | 1999-06-15 | 2004-03-30 | Bristol-Myers Squibb Pharma Company | Substituted heterocycle fused gamma-carbolines |
| US7071186B2 (en) | 1999-06-15 | 2006-07-04 | Bristol-Myers Squibb Pharma Co. | Substituted heterocycle fused gamma-carbolines |
| AU2085502A (en) | 2000-11-30 | 2002-06-11 | Molecular Skincare Ltd | Diagnosis and treatment of disease |
| JP5010784B2 (en) | 2001-05-16 | 2012-08-29 | 独立行政法人科学技術振興機構 | Oligodendrocyte developmental disorder model non-human animal |
| US20080027353A1 (en) * | 2006-07-31 | 2008-01-31 | Kliman Harvey J | Method of making and using a library of biological information |
| US8355927B2 (en) | 2010-11-05 | 2013-01-15 | Genomind, Llc | Neuropsychiatric test reports |
| US9611292B2 (en) * | 2011-04-27 | 2017-04-04 | The Board Of Regents Of The University Of Texas System | Peptide inhibitors of serotonin 5-HT2c receptors:PTEN interaction |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4985352A (en) * | 1988-02-29 | 1991-01-15 | The Trustees Of Columbia University In The City Of New York | DNA encoding serotonin 1C (5HT1c) receptor, isolated 5HT1c receptor, mammalian cells expressing same and uses thereof |
| FR2696749B1 (en) * | 1992-10-14 | 1994-11-10 | Inst Nat Sante Rech Med | New polypeptides having serotonergic receptor activity, nucleic acids encoding these polypeptides and uses. |
-
1994
- 1994-09-21 US US08/310,271 patent/US5654139A/en not_active Expired - Lifetime
-
1995
- 1995-09-21 CA CA002199470A patent/CA2199470A1/en not_active Abandoned
- 1995-09-21 JP JP8511070A patent/JPH11507802A/en active Pending
- 1995-09-21 WO PCT/US1995/012002 patent/WO1996009386A2/en not_active Application Discontinuation
- 1995-09-21 EP EP95935029A patent/EP0782618A2/en not_active Withdrawn
- 1995-09-21 AU AU37203/95A patent/AU693944B2/en not_active Ceased
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