DNA encoding SNORF25 receptor
This invention provides isolated nucleic acids encoding mammalian SNORF25 receptors, purified mammalian SNORF25 receptors, vectors comprising nucleic acid encoding mammalian SNORF25 receptors, cells comprising such vectors, antibodies directed to mammalian SNORF25 receptors, nucleic acid probes useful for detecting nucleic acid encoding mammalian SNORF25 receptors, antisense oligonucleotides complementary to unique sequences of nucleic acid encoding mammalian SNORF25 receptors, transgenic, nonhuman animals which express DNA encoding normal or mutant mammalian SNORF25 receptors, methods of isolating mammalian SNORF25 receptors, methods of treating an abnormality that is linked to the activity of the mammalian SNORF25 receptors, as well as methods of determining binding of compounds to mammalian SNORF25 receptors, methods of identifying agonists and antagonists of SNORF25 receptors, and agonists and antagonists so identified.
1. A process for determining whether a chemical compound specifically binds to and activates a mammalian SNORF25 receptor, which comprises contacting cells producing a second messenger response and expressing on their cell surface the mammalian SNORF25 receptor, wherein such cells do not normally express the mammalian SNORF25 receptor, with the chemical compound under conditions suitable for activation of the mammalian SNORF25 receptor, and measuring the second messenger response in the presence and in the absence of the chemical compound, a change in the second messenger response in the presence of the chemical compound indicating that the compound activates the mammalian SNORF25 receptor; wherein
(1) the mammalian SNORF25 receptor has an amino acid sequence greater than 95% identical to the amino acid sequence shown in SEQ ID NO: 2 or that encoded by the plasmid pEXJT3T7-hSNORF25 (ATCC Accession No. 203495); or
2) the mammalian SNORF25 receptor has an amino acid sequence greater than 95% identical to the amino acid sequence shown in SEQ ID NO: 4 or that encoded by the plasmid pcDNA3.1-rSNORF25 (ATCC Accession No. 203494); or
3) the mammalian SNORF25 receptor has an amino acid sequence greater than 95% identical to the amino acid sequence shown in SEQ ID NO: 25 or that encoded by the plasmid pEXJ-mSNORF25-f (ATCC Patent Depository No. 2263).
2. The process of claim 1 , wherein the second messenger response comprises chloride channel activation and the change in second messenger is an increase in the level of chloride current.
3. The process of claim 1 , wherein, the second messenger response comprises change in intracellular calcium levels and the change in second messenger is an increase in the measure of intracellular calcium.
4. The process of claim 1 , wherein the second messenger response comprises release of inositol phosphate and the change in second messenger is an increase in the level of inositol phosphate.
5. A process for determining whether a chemical compound specifically binds to and inhibits activation of a mammalian SNORF25 receptor, which comprises separately contacting cells producing a second messenger response and expressing on their cell surface the mammalian SNORF25 receptor, wherein such cells do not normally express the mammalian SNORF25 receptor, with both the chemical compound and a second chemical compound known to activate the mammalian SNORF25 receptor, and with only the second chemical compound, under conditions suitable for activation of the mammalian SNORF25 receptor, and measuring the second messenger response in the presence of only the second chemical compound and in the presence of both the second chemical compound and the chemical compound, a smaller change in the second messenger response in the presence of both the chemical compound and the second chemical compound than in the presence of only the second chemical compound indicating that the chemical compound inhibits activation of the mammalian SNORF25 receptor; wherein
(1) the mammalian SNORF25 receptor has an amino acid sequence greater than 95% identical to the amino acid sequence shown in SEQ ID NO: 2 or that encoded by the plasmid pEXJT3T7-hSNORF25 (ATCC Accession No. 203495); or
2) the mammalian SNORF25 receptor has an amino acid sequence greater than 95% identical to the amino acid sequence shown in SEQ ID NO: 4 or that encoded by the plasmid pcDNA3.1-rSNORF25 (ATCC Accession No. 203494); or
3) the mammalian SNORF25 receptor has an amino acid sequence greater than 95% identical to the amino acid sequence shown in SEQ ID NO: 25 or that encoded by the plasmid pEXJ-mSNORF25-f (ATCC Patent Depository No. 2263).
6. The process of claim 5 , wherein the second messenger response comprises chloride channel activation and the change in second messenger response is a smaller increase in the level of chloride current in the presence of both the chemical compound and the second chemical compound than in the presence of only the second chemical compound.
7. The process of claim 5 , wherein the second messenger response comprises change in intracellular calcium levels and the change in second messenger response is a smaller increase in the measure of intracellular calcium in the presence of both the chemical compound and the second chemical compound than in the presence of only the second chemical compound.
8. The process of claim 5 , wherein the second messenger response comprises release of inositol phosphate and the change in second messenger response is a smaller increase in the level of inositol phosphate in the presence of both the chemical compound and the second chemical compound than in the presence of only the second chemical compound.
9. The process of any of claims 1 , 2 , 3 , 4 , 5 , 6 , 7 , or 8 , wherein the mammalian SNORF25 receptor is a human SNORF25 receptor, a rat SNORF25 receptor, or a mouse SNORF25 receptor.
10. The process of any of claims 1 , 2 , 3 , 4 , 5 , 6 , 7 , or 8 , wherein the cell is an insect cell.
11. The process of any of claims 1 , 2 , 3 , 4 , 5 , 6 , 7 , or 8 , wherein the cell is a mammalian cell.
12. The process of claim 11 , wherein the mammalian cell is nonneuronal in origin.
13. The process of claim 12 , wherein the nonneuronal cell is a COS-7 cell, CHO cell, 293 human embryonic kidney cell, NIH-3T3 cell or LM(tk−) cell.
14. The process of claim 1 or 5 , wherein the mammalian SNORF25 receptor is a constitutively active receptor.