WO1996037607A2 - Acide nucleique pourvu du domaine polymorphe d'un gene de recepteur de bradykinine b¿2? - Google Patents
Acide nucleique pourvu du domaine polymorphe d'un gene de recepteur de bradykinine b¿2? Download PDFInfo
- Publication number
- WO1996037607A2 WO1996037607A2 PCT/DE1996/000891 DE9600891W WO9637607A2 WO 1996037607 A2 WO1996037607 A2 WO 1996037607A2 DE 9600891 W DE9600891 W DE 9600891W WO 9637607 A2 WO9637607 A2 WO 9637607A2
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- WO
- WIPO (PCT)
- Prior art keywords
- dna
- bradykinin receptor
- polymorphic
- receptor gene
- polymorphic region
- Prior art date
Links
- 108020004707 nucleic acids Proteins 0.000 title abstract description 9
- 102000039446 nucleic acids Human genes 0.000 title abstract description 9
- 150000007523 nucleic acids Chemical class 0.000 title abstract description 9
- 101710085045 B2 bradykinin receptor Proteins 0.000 title abstract 2
- 108050001736 Bradykinin receptor Proteins 0.000 claims description 23
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 7
- 229920001184 polypeptide Polymers 0.000 claims description 6
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 238000003745 diagnosis Methods 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims 2
- 239000013613 expression plasmid Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 108020004414 DNA Proteins 0.000 description 23
- 108700028369 Alleles Proteins 0.000 description 17
- 201000010099 disease Diseases 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 102000010183 Bradykinin receptor Human genes 0.000 description 9
- 101800004538 Bradykinin Proteins 0.000 description 7
- 102400000967 Bradykinin Human genes 0.000 description 7
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 7
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 7
- 239000008280 blood Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 5
- 125000003729 nucleotide group Chemical group 0.000 description 5
- 239000013604 expression vector Substances 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 101000829171 Hypocrea virens (strain Gv29-8 / FGSC 10586) Effector TSP1 Proteins 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- OSBLTNPMIGYQGY-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid;boric acid Chemical compound OB(O)O.OCC(N)(CO)CO.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O OSBLTNPMIGYQGY-UHFFFAOYSA-N 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 239000008051 TBE buffer Substances 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 2
- 229960005542 ethidium bromide Drugs 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 208000000509 infertility Diseases 0.000 description 2
- 230000036512 infertility Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 206010007522 Cardiac asthma Diseases 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- 108010077861 Kininogens Proteins 0.000 description 1
- 102000010631 Kininogens Human genes 0.000 description 1
- 108010093008 Kinins Proteins 0.000 description 1
- 102000002397 Kinins Human genes 0.000 description 1
- 208000004327 Paroxysmal Dyspnea Diseases 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- -1 RNA and DNA Chemical class 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000014384 Type C Phospholipases Human genes 0.000 description 1
- 108010079194 Type C Phospholipases Proteins 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 208000021267 infertility disease Diseases 0.000 description 1
- 108091070195 kinin family Proteins 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/72—Receptors; Cell surface antigens; Cell surface determinants for hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Definitions
- the present invention relates to a nucleic acid comprising a polymorphic region of a B 2 bradykinin receptor gene, a method for producing such a nucleic acid and the use thereof.
- Bradykinin is a vasoactive nonapeptide of the kinin family, which is released from kininogens by proteolytic activity of kallikrein. Bradykinin is involved in various physiological processes such as cardiovascular hemostasis, neurotransmission, cell proliferation or bronchopulmonary contraction.
- bradykinin works via a cell surface receptor, which is called the B 2 bradykinin receptor. This receptor binds to G proteins and triggers, among other things, the activation of phospholipase C and / or phospholipase A.
- Studies of the genomic structure of the human B 2 bradykinin receptor gene show that it comprises 3 exons.
- bradykinin plays a role in various diseases and is present in different amounts. For example, the amount of bradykinin increases in heart disease and asthma and decreases in allergies.
- the present invention is therefore based on the object of providing a means by which it can be determined whether the B 2 bradykinin receptor is present in different forms in the above diseases. According to the invention, this is achieved by the subject matter in the claims.
- the present invention thus relates to a nucleic acid comprising a polymorphic region of a B 2 bradykinin receptor gene.
- polymorphic region of a B 2 bradykinin receptor gene encompasses any region of a B 2 bradykinin receptor gene which can have a sequence polymorphism in individuals of a population, for example humans.
- nucleic acid encompasses any type of nucleic acid, e.g. RNA and DNA, the latter being preferred.
- RNA and DNA the latter being preferred.
- the present invention will now be described by way of example for DNA.
- the present invention is based on the applicant's knowledge that the B 2 - bradykinin receptor gene has polymorphic regions. This is evident from the applicant's recent work in which DNA from blood donors was examined for the B 2 bradykinin receptor gene. Frequently found polymorphic areas are shown in FIGS. 1-4.
- Figure 1 describes a DNA comprising a polymorphic region of exon 1 of a B 2 bradykinin receptor gene.
- the polymorphic region is located at nucleotide position 12 downstream of the transcription start site. It represents a tandem repeat polymorphism and is expressed, for example, in the alleles BE1-2G, BE1 -3G and BE1 -3T.
- BE1 -2G there are two units of the repeat GGTGGGGAC, while BE1-3G has three of these units.
- BE1-3T has three repeat units, two of which correspond to the above repeat and one has the sequence GGTGGTGAC.
- Figure 2 (A) describes a DNA comprising a polymorphic region of exon 2 of a B 2 bradykinin receptor gene.
- the polymorphic region is located at nucleotide position 181 of the cDNA. It represents a base polymorphism and is expressed, for example, in the alleles BE2-C and BE2-T.
- BE2-C there is a C, which leads to the codon CGT (Arg), while BE2-T has a T, which leads to the codon TGT (Cys).
- Figure 2 (B) shows the open reading frame (ORF) of the alleles BE2-C and BE2-T.
- Figure 3 describes a DNA comprising a polymorphic region of exon 3 of a B 2 bradykinin receptor gene.
- the polymorphic region is located in the 3'-untranslated region of exon 3. It represents a polymorphism of repeats with a consensus sequence, TGGA (A) GGGCTAGAACC, and is expressed, for example, in the alleles BE3-R48 and BE3-R35 off. There are 48 repeats in BE3-R48, while BE3-R35 has 35 repeats.
- Figure 4 describes a DNA comprising a polymorphic region of the exon 1 promoter region.
- the polymorphic region is located at nucleotide positions 675 and 1 1 53. It is a base polymorphism and is expressed e.g. in the BP-TC and BP-CT alleles.
- BP-TC has a T (625) and a Cd 153
- BP-CT has a C (675) and a T (1 1 53).
- the DNAs of Figures 1-4 are preferred embodiments of the present invention.
- the DNA of Fig. 3 was BE3-R35 / 1 or BE3-R48 / 1 and the DNA of Fig. 1 as BE1 -3T (Xba 7.0 / 2) at the DSM (German Collection of Microorganisms and Cell Cultures) filed under DSM 9927, DSM 9928 and DSM 9929 on April 20, 1995.
- DSM German Collection of Microorganisms and Cell Cultures
- a DNA according to the invention can be present in a vector or expression vector.
- examples of such are known to the person skilled in the art.
- these are e.g. pGEMEX, pUC derivatives, pGEX-2T and pET3b.
- yeast e.g. to call pY100 and Ycpadl
- animal cells e.g. pKCR, pEFBOS, cDM8 and pCEV4 must be specified.
- suitable cells around one, in an expression vector to express the present DNA according to the invention.
- suitable cells include the E. coli strains HB101, DH1, x1776, JM101, JM109 and BL21, the latter being preferred, the yeast strain Saccharomyces cerevisiae and the animal cells L, 3T3, FM3A, CHO, COS, Vero and HeLa .
- DNA according to the invention has to be inserted into an expression vector. He is also aware that this DNA can be inserted in conjunction with a DNA coding for another protein or peptide, so that the DNA according to the invention can be expressed in the form of a fusion protein.
- polymorphic regions can be detected in a B 2 bradykinin receptor gene. It is thus possible, for example, to determine whether the B 2 bradykinin receptor is present in different forms in various diseases, such as cardiac diseases, asthma and allergies.
- the above areas can be demonstrated by conventional methods. Reference is made to the example below.
- the polymorphic areas of Figures 1-3 are detected in B 2 -Bradykinin receptor genes from blood donors. A customary PCR method is carried out for this. The amplified DNA fragments are then compared with one another in the customary manner, for example by means of gel electrophoresis. The above polymorphic areas are detected at different frequencies.
- B 2 bradykinin receptors can be found which have changed in their gene or protein structure. This can be done via a DNA according to the invention or a polypeptide according to the invention.
- the receptors can then be tested for their activity in conventional methods. Such methods can also include the use of drugs such as angiotensin converting enzyme inhibitors, kinin receptor agonists or antagonists and bradykinin agonists or antagonists, whereby their effect on altered B 2 bradykinin receptors can be examined.
- drugs such as angiotensin converting enzyme inhibitors, kinin receptor agonists or antagonists and bradykinin agonists or antagonists, whereby their effect on altered B 2 bradykinin receptors can be examined.
- Antibodies to modified B 2 bradykinin receptors can also be produced. These antibodies are suitable for both diagnostic and therapeutic purposes. Polypeptides according to the invention can be used in a conventional manner for their production.
- the invention is illustrated by the following example.
- Genomic DNA was isolated from 179 randomly selected blood donors. This genomic DNA was used to detect polymorphic areas in the respective B 2 bradykinin receptor genes. For this purpose, a PCR method was carried out, the primer pairs chosen being those which enable the polymorphic regions indicated in FIGS. 1-3 to be amplified. The following primer pairs were used: for exon 1: BE 1 F (5 '-G CCCTTCAAAGATGAG CTG-3') and BE 1 R (5 '-
- BE2F (5'-CCATTTCTCCTCCCTGCTCGAG-3') and BE2R (5'-
- the PCR reaction had a total volume of 50 ⁇ ⁇ and contained 1 ⁇ g of genomic DNA, 50 ng of forward (F) and reverse (R) primer, 1, 25 U Taq polymerase, 200 ⁇ mol of each of the dNTPs and 1.5 mM MgCl 2 .
- the cycling conditions were initially 5 minutes at 94 ° C, followed by 1 minute at 94 ° C, 1 minute at 53 ° C and 1 minute at 72 ° C for 40 cycles and an end extension time of 5 minutes at 72 ° C.
- PCR products obtained were subjected to single-strand conformation polymorphism electrophoresis (SSCP electrophoresis).
- 5 ⁇ ⁇ of the PCR mixture were diluted with 15 ⁇ ⁇ formamide and denatured at 95 ° C. for 5 minutes.
- the SSCP gel was a 12% polyacrylamide gel buffered with 1 x TBE (85 mM Tris, 90 mM boric acid, 2 mM EDTA) and the electrophoresis was carried out in 1x TBE, at room temperature, with constant 120 volts for 24 hours.
- the polymorphic region of FIG. 1 is detected in the form of the alleles 2G, 3G and 3T.
- the PCR products (10 l) obtained were digested with 4 U Taql at 65 ° C. for 1 hour. This was followed by electrophoretic separation on a 2.5% MetaPhor TM agarose gel with 1 ⁇ TBE buffer containing 35 g / ml ethidium bromide at 100 V for 2 hours. The separation was made visible under UV light.
- the polymorphic region of FIG. 2 is detected in the form of two alleles.
- the one allele (C at nucleotide position 181) was cleaved twice by Taql, while the other allele (T at nucleotide position 181) is cleaved only once (cf. FIG. 6).
- the PCR products obtained (10 ⁇ ⁇ ) were applied directly to a 1% agarose gel and electrophoretically with 1 ⁇ TBE buffer containing 35 ⁇ g / ml ethidium bromide at 100 V 2 Hours separated. The separation was made visible under UV light. 7 shows the separation.
- the polymorphic region of FIG. 3 is detected in the form of the alleles R48, R35, RV1 and RV2.
- the latter alleles have an intermediate number of repeats and are underrepresented.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Toxicology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Endocrinology (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
L'invention concerne un acide nucléique pourvu d'un domaine polymorphe d'un gène de récepteur de bradykinine B2, le procédé de préparation d'un tel acide nucléique et son utilisation.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE1995118931 DE19518931C1 (de) | 1995-05-23 | 1995-05-23 | Nukleinsäure mit einem polymorphen Bereich eines B¶2¶-Bradykinin-Rezeptor-Gens |
DE19518931.0 | 1995-05-23 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO1996037607A2 true WO1996037607A2 (fr) | 1996-11-28 |
WO1996037607A3 WO1996037607A3 (fr) | 1997-01-16 |
Family
ID=7762681
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/DE1996/000891 WO1996037607A2 (fr) | 1995-05-23 | 1996-05-22 | Acide nucleique pourvu du domaine polymorphe d'un gene de recepteur de bradykinine b¿2? |
Country Status (2)
Country | Link |
---|---|
DE (1) | DE19518931C1 (fr) |
WO (1) | WO1996037607A2 (fr) |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2195678A1 (fr) * | 1994-07-27 | 1996-02-08 | Joseph A. Borkowski | Animaux transgeniques modifies par le recepteur b2 de la bradykinine |
-
1995
- 1995-05-23 DE DE1995118931 patent/DE19518931C1/de not_active Expired - Fee Related
-
1996
- 1996-05-22 WO PCT/DE1996/000891 patent/WO1996037607A2/fr active Application Filing
Also Published As
Publication number | Publication date |
---|---|
WO1996037607A3 (fr) | 1997-01-16 |
DE19518931C1 (de) | 1996-09-19 |
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