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US 2006/0242724 A1Published application
Receptor
OwnerMark Carlton, John Dixon +4inventors
InventorsMark Carlton, John Dixon, Alan Hendrick, Sophie Messager, Dirk Zahn, Jennifer Horwood
Life of this patent
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Abstract
The present invention relates to novel functions of a known receptor. In particular, the invention relates to the use of a sphingosylphosphorylcholine receptor and/or ligands thereof in the manipulation of the neuronal and limbic systems and diagnosis and treatment of pain.
Claims13
A transgenic animal comprising within at least a proportion of its cells, exogenous nucleic acid encoding one or more selected from the group consisting of:
- GPR12 polypeptide, one or more agonists of GPR12 polypeptide, one or more antagonists of GPR12 polypeptide and one or more modulators of GPR12 activity.
A nucleic acid construct suitable for functionally inactivating one or more endogenous GPR12 genes in a host cell comprising:
- (a) a non-homologous replacement region;
- (b) a first homology region located upstream of the non-homologous replacement region;
- (c) a mutated GPR12 gene and which when expressed does not encode functionally active GPR12;
- (d) a second homology region located downstream of the non-homologous replacement portion, the second homology region located downstream of the non-homologous replacement region, the second homology region having a nucleotide sequence exhibiting at least 90% identity to a second GPR12 gene.
1 more element
A method of identifying:
- (i) one or more antagonists of the functional activity of GPR12 polypeptide comprising the step of:
- (a) selecting one or more mammals comprising functionally active GPR12 polypeptide;
- (b) treating those one or more mammals with one or more potential antagonists of GPR12 polypeptide;
- (c) testing those one or more mammals to determine if those mammals exhibit one or more characteristics exhibited by GPR12 knockout mice and selected from the group consisting of the following:
- Alzheimer's and related diseases, Parkinson's disease, epilepsy and epileptogenic, dizziness and motion sickness, motor neuron disease, and diseases of neuronal dysfunctions, as well as pain including nociceptive pain and hyperanalgesia, hepatitis, muscle degradation, hypothyroidism, pancreatitis or MI, multiple myeloma, and diabetes;
- and
- (d) selecting those one or more antagonists which exhibit one or more of the characteristics according to step (c);
- or
- (ii) one or more molecules which agonise the functional activity of GPR12 polypeptide comprising the steps of:
- (a) selecting one or more mammals comprising functionally inactive GPR12 polypeptide;
- (b) treating those one or more mammals with one or more potential GPR12 mimics which potentially agonise at least on aspect of GPR12 activity;
- (c) testing those one or more mammals treated according to step (b) to determine if those treated mammals have one or more restored characteristics compared with those mammals selected according to step (a);
- and
- (d) selecting those one or more GPR12-ligand mimics which restore one or more characteristics of wild type mammals to those mammals selected according to step (a);
- or
- (iii) one or more molecules which antagonise the functional activity of GPR12 polypeptide comprising the steps of:
- (a) selecting one or more mammals comprising functionally active GPR12 polypeptide;
- (b) treating those one or more mammals with one or more potential GPR12 antagonists which potentially antagonise at least on aspect of GPR12 activity;
- and
- (c) testing those one or more mammals treated according to step (b) to determine if those treated mammals have one or more modulated characteristics compared with those mammals selected according to step (a).
17 more elements
A method for:
- (i) the diagnosis of a disease or condition selected from the group consisting of the following:
- Alzheimer's and related diseases, Parkinson's disease, epilepsy and epileptogenic, dizziness and motion sickness, motor neuron disease, and diseases of neuronal dysfunctions, as well as pain including nociceptive pain and hyperanalgesia, hepatitis, muscle degradation, hypothyroidism, pancreatitis or MI, multiple myeloma, and diabetes, comprising the steps of:
- (a) selecting a sample of cells from a patient to be diagnosed;
- and
- (b) comparing the expression levels and/or functional activity of GPR12 polypeptide in those sample of cells with one or more control sample/s from healthy individuals;
- or,
- (ii) the treatment of a condition in a patient selected from the group consisting of:
- Alzheimer's and related diseases, Parkinson's disease, epilepsy and epileptogenic, dizziness and motion sickness, motor neuron disease, and diseases of neuronal dysfunctions, as well as pain including nociceptive pain and hyperanalgesia, hepatitis, muscle degradation, hypothyroidism, pancreatitis or MI, multiple myeloma, and diabetes comprising the step of treating that patient with a therapeutically effective amount of one or more selected from the group consisting of:
- GPR12 polypeptide, one or more agonists of GPR12 polypeptide, one or more antagonists of GPR12 polypeptide and one or more modulators of GPR12 activity;
- or,
- (iii) manipulating neuronal proliferation and synaptic formation in a patient comprising the step of treating the patient with a therapeutically effective amount of one or more selected from the group consisting of:
- GPR12 polypeptide, one or more agonists of GPR12 polypeptide, one or more antagonists of GPR12 polypeptide and one or more modulators of GPR12 activity
9 more elements
Dependencies are inferred from the claim text.