Receptor
OwnerSamuel Aparicio, Mark Carlton +4inventors
InventorsSamuel Aparicio, Mark Carlton, John Dixon, Sophie Messager, Andreas Russ, Rosemary Thresher
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Abstract
We disclose BACH G-protein coupled receptor (GPCR) polypeptides comprising the amino acid sequence shown in SEQ ID NO: 3 or SEQ ID NO: 5, and homologues, variants and derivatives thereof. Nucleic acids capable of encoding BACH polypeptide are also disclosed, in particular, those comprising the nucleic acid sequences shown in SEQ ID NO: 1, SEQ ID NO: 2 or SEQ ID NO: 4 or a mouse BACH genomic sequence (SEQ ID NO:10).
Claims60
A BACH GPCR polypeptide comprising the amino acid sequence shown in SEQ ID NO. 3 or SEQ ID NO:
- 5, or a homologue, variant or derivative thereof.
A method for identifying an antagonist of a BACH GPCR, the method comprising contacting a cell which expresses BACH receptor with a candidate compound and determining whether the level of cyclic AMP (cAMP) in the cell is lowered as a result of said contacting.
A method for identifying a compound capable of lowering the endogenous level of cyclic AMP in a cell which method comprises contacting a cell which expresses a BACH GPCR with a candidate compound and determining whether the level of cyclic AMP (cAMP) in the cell is lowered as a result of said contacting.
A method of identifying a compound capable of binding to a BACH GPCR polypeptide, the method comprising contacting a BACH GPCR polypeptide with a candidate compound and determining whether the candidate compound binds to the BACH GPCR polypeptide.
A method of treating a patient suffering from a disease associated with enhanced activity of a BACH GPCR, which method comprises administering to the patient an antagonist of BACH GPCR.
A method of treating a patient suffering from a disease associated with reduced activity of a BACH GPCR, which method comprises administering to the patient an agonist of BACH GPCR.
25a. A method according to claim 24, in which the BACH GPCR comprises a polypeptide having the sequence shown in SEQ ID NO:
- 3 or SEQ ID NO:
- 5.
A non-human transgenic animal, characterised in that the transgenic animal comprises an altered BACH gene.
A non-human transgenic animal having a functionally disrupted endogenous BACH gene, in which the transgenic animal comprises in its genome and expresses a transgene encoding a heterologous BACH protein.
A nucleic acid construct for functionally disrupting a BACH gene in a host cell, the nucleic acid construct comprising:
- (a) a non-homologous replacement portion;
- (b) a first homology region located upstream of the non-homologous replacement portion, the first homology region having a nucleotide sequence with substantial identity to a first BACH gene sequence;
- and (c) a second homology region located downstream of the nonhomologous replacement portion, the second homology region having a nucleotide sequence with substantial identity to a second BACH gene sequence, the second BACH gene sequence having a location downstream of the first BACH gene sequence in a naturally occurring endogenous BACH gene.
A method of diagnosis of a disease or syndrome caused by or associated with increased, decreased or otherwise abnormal expression of BACH GPCR, the method comprising the steps of:
- (a) detecting the level or pattern of expression of BACH GPCR in an animal suffering or suspected to be suffering from such a disease;
- and (b) comparing the level or pattern of expression with that of a normal animal.
A nucleic acid comprising a sequence SEQ ID NO:
- 10.
A nucleic acid sequence selected from group consisting of
- 6 mBach 5′ pr F (GAGCTGAGGATGTAATCCTAGCACTTG), mBach 5′ pr R (CCTTCCTTACTAAACTGTGGGGCACTC), mBach 5′ scr (GGGTCACCACAACTGTATGAAAGAGTC), mBach 5′ arm F (AAACTCGAGAGGAAAGCTGAGAATCACTGCCTTGAG), mBach 5′ arm R (AAAACTAGTCGATAGTCAGGGCACTGGAGCACAGAG), mBach 3′ arm F (TTTGGCGCGCCTGAGGGAGGTGGGCTGGGTACTTGGAC), mBach 3′ arm R (AAAGGCCGGCCACCACCTTCTGCTTTCTCTTACCTTC), mBach 3′ pr F(AGGTTCGCAGACATGCTTGTAGGATAG), mBach 3′.pr R(GGGGCACTTTGTGAAAATGGCAGACTC), mBach +/− F(GCTCACCGAACTACCCTCAGAAAGCAC) and mBach +/− R (CCCTTCTGCACACTAGAGCTGGAGTTG).
Dependencies are inferred from the claim text.