Mammalian osteoregulins
AssigneePfizer Inc.
InventorsThomas A. Brown, Jeffrey R. De Wet, Lori C. Gowen, Lynn M. Hames
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Abstract
The invention features novel osteoregulin polypeptides, nucleic acid sequences which encode the polypeptides, vectors, antibodies, hosts which express heterologous osteoregulins, and animal cells and mammals with a targeted disruption of an osteoregulin gene. These osteoregulins play a role in regulating bone homeostasis, adiposity, and the calcification of atherosclerotic plaques. Accordingly, the invention also features screening assays to identify modulators of osteoregulin activity as well as methods of treating mammals for diseases or disorders associated with osteoregulin activity.
Claims33
An isolated or purified polypeptide comprising:
- (a) the amino acid sequence of SEQ ID NO:
- 2, 4, 6, 8, 34, or 46;
- or
- (b) an amino acid sequence encoded by a polynucleotide which will hybridize under highly stringent conditions with a probe having the complement of the coding sequence shown in SEQ ID NO:
- 1, 3, 5, 7, 33, or 45;
- wherein said polypeptide has osteoregulin activity.
An isolated or purified polypeptide comprising an amino acid sequence having at least 90% identity to an amino acid sequence comprising SEQ ID NO:
- 2, 4, 6, 8, 34, or 46, wherein said polypeptide has osteoregulin activity.
A heterologous polypeptide comprising:
- (a) the amino acid sequence of SEQ ID NO:
- 2, 4, 6, 8, 34, or 46;
- or
- (b) an amino acid sequence encoded by a polynucleotide which will hybridize under highly stringent conditions with a probe having the complement of the coding sequence shown in SEQ ID NO:
- 1, 3, 5, 7, 33, or 45;
- wherein said polypeptide has osteoregulin activity, and wherein said polypeptide is produced by expression of a heterologous polynucleotide in a host.
A heterologous polypeptide comprising an amino acid sequence having at least 90% identity to an amino acid sequence comprising SEQ ID NO:
- 2, 4, 6, 8, 34, or 46, wherein said polypeptide has osteoregulin activity, and wherein said polypeptide is produced by expression of a heterologous polynucleotide in a host.
A genetically-modified, non-human mammal, wherein the modification results in a functionally disrupted osteoregulin gene.
A genetically-modified animal cell, wherein the modification comprises a functionally disrupted osteoregulin gene.
A method of screening for an agent that modulates an osteoregulin activity, said method comprising contacting an agent with an osteoregulin polypeptide and measuring the activity of said osteoregulin, wherein a difference between said osteoregulin activity in the presence of the agent and in the absence of the agent is indicative that the agent modulates said activity.
A method of screening for an agent that modulates an osteoregulin activity by modulating osteoregulin expression, said method comprising contacting an agent with a cell containing a nucleotide sequence comprising an osteoregulin gene regulatory element operably linked to a coding sequence, and measuring the expression of said coding sequence, wherein a difference between said expression in the presence of the agent and in the absence of the agent is indicative that the agent modulates osteoregulin expression.
A method of treating a mammal to regulate bone mass and/or density, adiposity, vascular flexibility, and/or atherosclerotic plaque calcification, said method comprising administering an osteoregulin modulator to said mammal.
Dependencies are inferred from the claim text.