DNA endoding human alpha 1 adrenergic receptors

• US 5,861,309 A
• Filed: 08/21/1995
• Issued: 01/19/1999
• Est. Priority Date: 09/25/1992
• Status: Expired due to Term

• Current Assignee: H. Lundbeck A/S (Lundbeck Foundation)
• Original Assignee: Synaptic Pharmaceutical Corporation (Lundbeck Foundation)
• Inventors: Bard, Jonathan A., Weinshank, Richard L., Forray, Carlos
• Primary Examiner(s): LeGuyader, John L.
• Assistant Examiner(s): WANG, ANDREW J
• Application Number:
  US08/406,855
• Time in Patent Office: 1,247 Days
• Field of Search: 536/23.1, 536/23.5, 435/320.1, 435/325, 435/69.1, 435/172.3
• US Class Current: 435/325
• CPC Class Codes: A01K 2207/15 Humanized animals
• CPC Class Codes: A01K 2217/00 Genetically modified animals
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A01K 2227/10 Mammal
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/02 Animal zootechnically ameliorated
• CPC Class Codes: A01K 2267/03 Animal model, e.g. for test or diseases
• CPC Class Codes: A01K 2267/0393 Animal model comprising a reporter system for screening tests
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07K 14/70571 : for neuromediators, e.g. serotonin receptor, dopamine receptor
• CPC Class Codes: C12N 15/85 : for animal cells
• CPC Class Codes: C12N 15/8509 : for producing genetically modified animals, e.g. transgenic
• CPC Class Codes: C12Q 1/6876 : Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• CPC Class Codes: C12Q 1/6897 : involving reporter genes operably linked to promoters
• CPC Class Codes: C12Q 2600/158 : Expression markers
• CPC Class Codes: G01N 2500/10 : involving cells
• CPC Class Codes: G01N 33/9433 : (Nor)adrenaline

Abstract

This invention provides an isolated nucleic acid, vectors, transformed mammalian cells and non-human transgenic animals that encode and express normal or mutant alpha 1a, alpha 1b and alpha 1c adrenergic receptor genes. This invention also provides a protein, and an antibody directed to the protein and pharmaceutical compounds related to alpha 1a, alpha 1b and alpha 1c adrenergic receptors. This invention provides nucleic acid probes, and antisense oligonucleotides complementary to alpha 1a, alpha 1b and alpha 1c adrenergic receptor genes. This invention further provides methods for determining ligand binding, detecting expression, drug screening, and treatments for alleviating abnormalities associated with human alpha 1a, alpha 1b and alpha 1c adrenergic receptors.

Claims

1. An isolated nucleic acid molecule encoding a human α

_1a adrenergic receptor, wherein the α

_1a adrenergic receptor has an amino acid sequence as shown in SEQ ID No. 2.

3. The nucleic acid molecule of claim 1 or 2, wherein the nucleic acid molecule is a DNA molecule.

4. The DNA molecule of claim 3, wherein the DNA molecule is a cDNA molecule.

5. A vector comprising a DNA molecule of claim 3.

6. A plasmid comprising the vector of claim 5.

7. The vector of claim 5 adapted for expression in a bacterial cell which comprises the regulatory elements necessary for expression of the DNA in a bacterial cell so located relative to the DNA encoding a human α

₁ adrenergic receptor as to permit expression thereof.

8. The vector of claim 5 adapted for expression in a yeast cell which comprises the regulatory elements necessary for the expression of the DNA in a yeast cell so located relative to the DNA encoding a human α

₁ adrenergic receptor as to permit expression thereof.

9. The vector of claim 5 adapted for expression in a mammalian cell which comprises the regulatory elements necessary for expression of the DNA in the mammalian cell so located relative to the DNA encoding a human α

₁ adrenergic receptor as to permit expression thereof.

10. The plasmid of claim 6 adapted for expression in a mammalian cell which comprises the regulatory elements necessary for expression of the DNA in the mammalian cell so located relative to the DNA encoding a human α

₁ adrenergic receptor as to permit expression thereof.

13. A mammalian cell comprising the plasmid of claim 6.

14. The mammalian cell of claim 13, wherein the mammalian cell is an LM (tk-) cell.

15. An LM (tk-) cell comprising the plasmid of claim 10.

2. An isolated nucleic acid molecule encoding a human α

_1b adrenergic receptor, wherein the α

_1b adrenergic receptor has an amino acid sequence as shown in SEQ ID No. 4.

11. A plasmid designated pcEXV-α

_1a.

12. A plasmid designated pcEXV-α

_1b.