Transgenic animal
AssigneeWyeth, a Delaware corporation
InventorsKathleen Young, David S. Howland, Karen L. Marquis, Sharon Rosenzweig-Lipson, Mark Ian Cockett
Life of this patent
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Abstract
A transgenic rat containing in its genome a nucleotide sequence encoding a Ga subunit protein, which Ga protein subunit is uncoupled from regulation by Regulators of G-Protein Signaling (RGS) proteins, which Gx subunit protein is eventually the dominant-negative G188S mutant of Gax9, which nucleotide sequence is operatively associated with a neuron-specific expression control sequence, wherein the transgenic rat expresses the GA subunit protein in neural cells resulting in extended D-protein coupled receptor signaling mediated by the Ga subunit protein.
Claims23
1-22. (canceled)
A transgenic animal containing in its genome a nucleotide sequence encoding a mutant Gα subunit protein, wherein said transgenic animal is not a human, and wherein said mutant Gα subunit protein is uncoupled from regulation by Regulators of G-protein Signaling (RGS) proteins, which nucleotide sequence is operatively associated with a neuron-specific expression control sequence, wherein the transgenic animal expresses the Gα subunit protein in neural cells resulting in extended G-protein coupled receptor signaling mediated by the Gα subunit protein.
A transgenic animal containing in its genome a nucleotide sequence encoding a mutant Gαq subunit protein, wherein said transgenic animal is not a human, wherein said mutant Gαq subunit protein has glycine 188 substituted with serine (G188S) and wherein said mutant Gαq subunit protein is uncoupled from regulation by Regulators of G-protein Signaling (RGS) proteins, said nucleotide sequence being operatively linked with a neuron-specific expression control sequence, wherein the transgenic animal expresses the Gαq subunit protein in neural cells resulting in extended G-protein coupled receptor signaling mediated by the Gαq subunit protein, and wherein said transgenic animal exhibits a phenotype selected from the group consisting of vibration as assessed by global behavior assessment;
- increased center return time as assessed by an open field test;
- decreased contextual fear conditioning;
- decreased food intake;
- decreased body weight;
- increased sensitivity to 5-HT2A agonists and 5-HT2C agonists;
- increased cholinergic signs in response to muscarinic agonists;
- decreased prepulse inhibition;
- increased hyperactivity in response to N-methyl D-aspartate (NMDA) antagonists;
- and decreased hyperactivity in response to dopamine (DA) agonists, as compared to a wild type control.
A method for generating a transgenic animal that has extended GPCR signaling, which method comprises introducing a nucleotide sequence encoding a Gα subunit protein into the genome of the animal, which Gα protein subunit is uncoupled from regulation by RGS proteins, which nucleotide sequence is operatively associated with a neuron-specific expression control sequence, whereby the transgenic animal expresses the Gα subunit protein in neural cells resulting in extended GPRC signaling.
Dependencies are inferred from the claim text.