Modulating ramp activity
AssigneePfizer Inc.
InventorsJohn D. McNeish, Walter C. Soeller, John F. Thompson
Life of this patent
Estimating the term…
Abstract
The invention provides genetically-modified non-human mammals and genetically-modified animal cells containing a disrupted RAMP1, RAMP2, or RAMP3 gene. Also provided by the invention are methods of screening for agents that modulate the activity or expression of a RAMP and methods of treating mammals to modulate liver function and/or muscle metabolism.
Claims14
A genetically-modified, non-human mammal, wherein the genetic modification results in a disrupted RAMP1 or RAMP3 gene.
A genetically-modified, non-human mammal, wherein said mammal is heterozygous for a genetic modification which results in a disrupted RAMP2 gene and results in expression of an exogenous reporter gene under the control of the regulatory sequences of said RAMP2 gene.
A genetically-modified animal cell, wherein the modification comprises a disrupted RAMP1, RAMP2, or RAMP3 gene.
A membrane preparation derived from a genetically-modified animal cell comprising a disrupted RAMP1, RAMP2, or RAMP3 gene.
A method of treating a disorder associated with liver function and/or muscle metabolism in a mammal, said method comprising administering an agent that modulates RAMP1 activity.
A method of identifying an agent that modulates RAMP1, RAMP2, or RAMP3 activity, said method comprising:
- (a) contacting said agent with a mammalian cell from the female or male reproductive tract, or the skin, and measuring RAMP1 activity;
- (b) contacting said agent with a mammalian spermatogenic cell, and measuring RAMP2 activity;
- or
- (c) contacting said agent with a mammalian cell from the caudate putamen, the laterodorsal thalamic region of the cerebrum, or the male reproductive tract, and measuring RAMP3 activity;
- wherein a difference between said activity in (a), (b), or (c), in the absence of the agent and in the presence of the agent is indicative that the agent can modulate RAMP1, RAMP2, or RAMP3 activity, respectively.
A method of identifying an agent that modulates RAMP1, RAMP2, or RAMP3 gene expression, said method comprising:
- (a) contacting an agent with a mammalian cell from the female or male reproductive tract, or the skin, that expresses a coding sequence under the control of RAMP1 gene regulatory sequences, and measuring expression of said coding sequence;
- (b) contacting an agent with a mammalian spermatogenic cell that expresses a coding sequence under the control of RAMP2 gene regulatory sequences, and measuring expression of said coding sequence;
- or
- (c) contacting an agent with a mammalian cell from the caudate putamen, the laterodorsal thalamic region of the cerebrum, or the male reproductive tract, that expresses a coding sequence under the control of RAMP3 gene regulatory sequences, and measuring expression of said coding sequence,
- wherein a difference between said expression in (a), (b), or (c), in the absence of the agent and in the presence of the agent is indicative that the agent can modulate RAMP1, RAMP2, or RAMP3 gene expression, respectively.
Dependencies are inferred from the claim text.